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  • calcium  (147)
  • hypertension  (146)
  • Springer  (293)
  • 2020-2024
  • 2015-2019
  • 1985-1989  (293)
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  • 101
    Electronic Resource
    Electronic Resource
    Effects of BAYl 5240, a fixed combination of low dose nifedipine and acebutolol on hypertension: Comparison with standard dose nifedipine (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 17-21 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; acebutolol ; hypertension ; combination therapy ; double-blind study ; adverse effects ; BAYl 5240
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 116 patients from 4 clinics participated in a double blind study to assess the efficacy of (BAYl 5240), a nifedipine-acebutolol fixed combination (10 mg+100 mg), as compared to nifedipine 20 mg in essential hypertension. During the 10 week study, the mean recumbent blood pressure decreased 1 to 3 h after treatment from 175.5/105.2 to 148.3/88.0 mmHg in the BAY1 5240 group and from 174.3/102.9 to 150.3/86.5 mmHg in the nifedipine group. The results also showed a comparable decrease in the mean systolic (SBP) and diastolic (DBP) blood pressures before treatment (24 h after last tablet) and after physical exertion before and after either drug given for 4 weeks. Doubling of the dose for 4 additional weeks produced a moderate and similar additional decrease in blood pressure. The results show the possibility of treating essential hypertension with a low dose of a beta-adrenergic blocking agent in combination with 10 mg nifedipine. Both regimens were well tolerated. One patient in the BAYl 5240 group and 2 in the nifedipine group, all treated by the same investigator, were withdrawn from the study because of headache during the nifedipine pre-period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635702
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  • 102
    Electronic Resource
    Electronic Resource
    Bromocriptine reduces plasma noradrenaline and 3,4-dihydroxyphenylacetic acid in normal and hypotensive subjects (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 671-675 
    Details
    ISSN: 1432-1041
    Keywords: bromocriptine ; hypertension ; plasma catecholamines ; 3,4-dihydroxyphenylacetic acid ; peripheral dopamine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a single oral dose of bromocriptine 2.5 mg was evaluated in 11 normotensive and 6 hypertensive volunteers. 150 min after drug administration, a significant decrease in plasma noradrenaline concentration from 202 to 124 pg/ml in normotensive and from 197 to 119 pg/ml in hypertensive patients was observed. Plasma 3,4 dihydroxyphenylacetic acid, a major metabolite of dopamine, fell from 1132 to 956 pg/ml in normal subjects and from 1242 to 807 pg/ml in hypertensives. No change in plasma adrenaline was found. At the same time, mean arterial pressure showed a significant decrease from 90 to 81 and from 132 to 111 mmHg in normotensive and hypertensive subjects, respectively. Bromocriptine also inhibited the increase in noradrena-line level that occurred when the subjects changed from the supine to the standing position. The inhibition was more evident in hypertensive subjects. It is suggested that the hypotensive effect of bromocriptine is mediated by the inhibition of noradrenaline release due to the stimulation of dopamine receptors on noradrenergic nerve terminals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547047
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  • 103
    Electronic Resource
    Electronic Resource
    Effects of a new diuretic piretanide on glucose tolerance, insulin secretion and 125I-insulin binding (1985)
    Springer
    European journal of clinical pharmacology 27 (1985), S. 697-700 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; hypertension ; glucose tolerance ; loop diuretics ; insulin secretion ; insulin binding ; C-peptide ; glycohaemoglobin A1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a new diuretic, piretanide, on glucose tolerance, insulin secretion and 125I-insulin binding to erythrocytes was studied in 12 male patients with mild essential hypertension. After a 4 week wash-out period with placebo, piretanide 6 mg b.i.d. was administered in a single-blind manner for 8 consecutive weeks. Although glucose tolerance deteriorated slightly in one patient, the diuretic treatment had no effect on the mean blood glucose concentrations during oral glucose tolerance tests or on glyco-haemoglobin A1 measurements, both studies being done at 4 week intervals. Preservation of euglycemia was associated with increased insulin secretion. After 8 weeks of piretanide therapy the basal C-peptide concentration was 61% higher than the pretreatment level (0.44 vs 0.71 µU/ml; p〈0.05). Glucagon — stimulated C-peptide concentrations were significantly elevated after 4 (1.67 vs 2.53 µU/ml, p〈0.05) and after 8 weeks (1.67 vs. 2.90 µU/ml, p〈0.01) of diuretic treatment. Fasting plasma immunoreactive insulin (IRI) levels were virtually unchanged by the drug therapy. The enhanced insulin secretion did not appear secondary to increased insulin resistance at the insulin receptor level, since the specific bound fraction of 125I-insulin remained unaffected by diuretic treatment. Although short-term loop diuretic treatment appears to have no effect on glucose tolerance, the very low density lipoprotein synthetic rate may be promoted by the increased insulin secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547052
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  • 104
    Electronic Resource
    Electronic Resource
    Cold sensitivity in essential hypertension: the effect of beta- and combined alpha- and beta-blockade (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 33-36 
    Details
    ISSN: 1432-1041
    Keywords: cold sensitivity ; hypertension ; alpha- and beta-blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The presence of cold sensitivity was investigated in three groups of patients; untreated hypertensives and hypertensives treated by a beta-adrenoceptor blocker (propranolol) or by a combined alpha-and beta-adrenoceptor blocker (labetalol) at two ambient temperatures. At a comfortable ambient (24°C) one-third of the untreated and those treated with beta-blockade only showed cold sensitivity as compared with 16% of patients on the combined therapy. Under conditions of mild cold stress (20°C) cold sensitivity increased in frequency in all three groups, more than half of the untreated and beta-blocked patients were affected and greater than one-third of those with alpha- and beta-blockade. These findings indicate that in the general population of hypertensives treatment with beta-adrenoceptor blockade alone may have little effect on the peripheral vasculature and that a useful degree of protection may be provided by therapy which blocks both receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547365
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  • 105
    Electronic Resource
    Electronic Resource
    Haemodynamic effects of enalapril, a new converting enzyme inhibitor, in hypertensive patients (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 17-20 
    Details
    ISSN: 1432-1041
    Keywords: enalapril ; ACE inhibitor ; hypertension ; haemodynamic effects ; renin-angiotensin system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The haemodynamic effects of enalapril (EN), a new, long-acting, nonsulphhydryl converting enzyme inhibitor, were evaluated by non-invasive methods in 10 adult patients with mild to moderate essential hypertension (EH). Patients were randomly assigned, double blind to 2 treatment groups (EN 20 mg o.d. or 10 mg b.d.) for 4 weeks, and were crossed over to the other dosage regimen after a 2-week washout period. Measurements included mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), limb blood flow (LBF), plasma aldosterone (ALD), plasma renin activity (PRA) and systolic time intervals (STI). Both regimens (b.d. and o.d.) significantly reduced MAP (15.3% and 16.3%, respectively), total peripheral resistance (20.3% and 21.8%, respectively), limb vascular resistance (24.1% and 24.9%) and ALD (33.5% and 36.9%) and increased CO (7.8% and 8.7%), LBF (10.9% and 11.6%) and PRA (10.4% and 9.5%). No significant change was observed in HR or STI. EN 20 mg o.d. or 10 mg b.d. reduced arterial pressure to a similar extent through a fall in total peripheral resistance. An increase in CO was also observed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547362
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  • 106
    Electronic Resource
    Electronic Resource
    The pharmacodynamics and pharmacokinetics of a new calcium antagonist nisoldipine in normotensive and hypertensive subjects (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 21-24 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; nifedipine ; pharmacokinetics ; pharmacodynamics ; calcium channel blocking drugs ; hypertension ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic and pharmacokinetic profiles of nifedipine and nisoldipine were compared in a double blind, placebo-controlled study. Nisoldipine, 10 mg significantly reduced systolic blood pressure but nifedipine 20 mg retard did not, although both drugs had significant pharmacodynamic effects as evidenced by increased heart rates. The terminal elimination half-life in plasma was similar for both drugs with a mean of 2 h. The pharmacodynamics of nisoldipine were studied in 8 hypertensives following both acute and chronic administration. Antihypertensive efficacy was demonstrated after acute dosing and was maintained over 4 weeks of twice daily treatment as monotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547363
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  • 107
    Electronic Resource
    Electronic Resource
    Effects of the dopaminergic agonist cianergoline on blood pressure, the renin-angiotensin-aldosterone axis and the sympathetic nervous system in patients with essential hypertension (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 25-31 
    Details
    ISSN: 1432-1041
    Keywords: cianergoline ; hypertension ; dopaminergic agonist ; renin angiotensin aldosterone ; lipid metabolism ; benign essential hypertension ; side-effects ; prolactin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cianergoline is a new dopaminergic agonist with a predominant cardiovascular action. Its effects on blood pressure, the renin-angiotensin-aldosterone axis, the sympathetic nervous system and lipid metabolism were assessed in 20 patients with benign essential hypertension. Cianergoline given in increasing doses for 4 weeks (maximum daily dose 12±2 mg (SD)) and placebo both caused a slight decrease in arterial pressure, (from 159/104 to 152/98 mm Hg and from 154/104 to 149/103 mm, respectively; difference not significant). Supine and upright plasma renin activity, plasma aldosterone, norepinephrine, epinephrine and dopamine levels, urinary catecholamine excretion rates as well as serum prolactin, low and high density cholesterol and triglyceride concentrations were not changed after cianergoline or placebo. Total serum cholesterol and triglyceride levels decreased significantly after placebo, but were unchanged after cianergoline. 3 out of 10 patients in the cianergoline group complained of nausea. The findings indicate that the new dopaminergic agonist cianergoline exerts only a mild blood pressure lowering effect in patients with essential hypertension and does not modify the release of prolactin, lipid metabolism or the basal activity or postural responsiveness of the renin-angiotensin-aldosterone axis and of the sympathetic nervous system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00547364
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  • 108
    Electronic Resource
    Electronic Resource
    Blood pressure and catecholamines following exercise during selective beta-blockade in hypertension (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 283-287 
    Details
    ISSN: 1432-1041
    Keywords: beta-blockers ; hypertension ; catecholamines ; exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study examines and compares the hemodynamic and sympathoadrenal response to bicycle exercise in hypertensive subjects during two weeks' treatment with a cardio-selective (metoprolol) and nonselective (propranolol) beta-blocker. The increase in plasma norepinephrine and epinephrine concentration following exercise was augmented to a similar degree with each beta-blocker. Pre-exercise blood pressure and heart rate were similar for the two drugs. However immediately after exercise and particularly after resting for 20 min post exercise, diastolic blood pressure was lower during metoprolol treatment. Systolic blood pressure was also lower 20 min post exercise during metoprolol treatment. These observations indicate that cardio-selective beta-blockers offer advantages in blood pressure control during exercise through intact vascular β2-adrenoceptors opposing sympathetically mediated vasoconstriction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541529
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  • 109
    Electronic Resource
    Electronic Resource
    Effect of verapamil on renal plasma flow, glomerular filtration rate and plasma angiotensin II, aldosterone and arginine vasopressin in essential hypertension (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 257-261 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; hypertension ; renal haemodynamics ; glomerular filtration ; arginine vasopressin ; renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal plasma flow, glomerular filtration rate plasma angiotensin II, aldosterone and arginine vasopressin, free water clearance, blood pressure and body weight in 11 patients with mild to moderate hypertension were determined at the end of consecutive 6 week periods of administration of placebo and verapamil up to 120 mg t.i.d. Verpamil induced a 10% reduction in diastolic blood pressure. Compared with placebo none of the other parameters measured changed after treatment with verapamil. There was no significant correlation between blood pressure and arginine vasopressin in plasma. It is concluded that verapamil reduced blood pressure by vasodilatation without activation of the counterbalancing mechanisms commonly seen after treatment with vasodilating drugs, i.e. tachycardia, activation of the renin-angiotensin-aldosterone system, water and salt retention, and without affecting renal haemodynamics. AVP does not seem to be involved in blood pressure regulation in mild to moderate essential hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544077
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  • 110
    Electronic Resource
    Electronic Resource
    The influence of alpha1-adrenergic blockade on the acute antihypertensive effect of nifedipine (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 263-267 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; prazosin ; hypertension ; alpha1-adrenergic blockade ; calcium antagonism ; vasodilatation ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The hypotensive effect of vasodilator monotherapy in hypertension is attenuated by a baroreceptor-mediated increase in the sympathetic release of noradrenaline. Nifedipine induces a rise in noradrenaline release, but it is not known to affect noradrenaline-induced vascular contraction of smooth muscle to a clinically significant degree. The haemodynamic and hormonal effects of a single sublingual dose of nifedipine 20 mg in 8 moderately hypertensive patients have been studied before and during postsynaptic alpha1-blockade with prazosin. The antihypertensive effect of nifedipine was significantly increased by prazosin pretreatment (fall in mean arterial pressure 60 min after nifedipine: −16.7% with and −8.5% without prazosin), despite similar increases in plasma noradrenaline. Prazosin alone caused no change in supine blood pressure for 2 h after an oral dose of 2 mg. The findings are in keeping with the hypothesis that prazosin blocks a compensatory reaction to vasodilatation caused by nifedipine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544078
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  • 111
    Electronic Resource
    Electronic Resource
    Single and divided daily dose piretanide in the treatment of uncomplicated essential hypertension: A double-blind comparison with a combination of hydrochlorothiazide and amiloride (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 269-273 
    Details
    ISSN: 1432-1041
    Keywords: piretanide ; hypertension ; hydrochlorothiazide/amiloride ; serum potassium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a randomised double blind study in patients with mild to moderate hypertension, piretanide 6 mg once and twice daily significantly reduced both supine and erect blood pressure. This was seen after only 2 weeks and a further progressive reduction was evident over the ensuing 12-week trial period. The higher dose produced a mean maximal fall of 29% in supine diastolic pressure, compared with 23% after the lower dose; the difference is not significant. Hydrochlorothiazide 50 mg/amiloride 5 mg twice daily (HCT/A) also reduced supine blood pressure significantly after 2 weeks, but the reduction in erect diastolic blood pressure did not achieve statistical significance until 8 weeks. The maximal effect (a 13% fall in supine diastolic blood pressure) was significantly less than that of either piretanide regimen. Blood pressures in this group also returned more rapidly to pretreatment levels during the placebo washout phase at the end of the study. HCT/A produced a significant sustained rise in serum potassium and a reduction in serum sodium and chloride. Piretanide had minimal effects on serum electrolytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544079
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  • 112
    Electronic Resource
    Electronic Resource
    Multicentre comparison of the antihypertensive effect of acebutolol and hydrochlorothiazide in uncomplicated mild-moderate hypertension in the elderly (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 275-279 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; acebutolol ; hydrochlorothiazide ; elderly ; cross-over trial ; blood pressure reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the efficacy of acebutolol, 400–600 mg/day in elderly hypertensive patients, and to compare it with hydrochlorothiazide 25–50 mg/day, 45 patients with mild-moderate uncomplicated hypertension were treated for 6 weeks in a multicentre, single-blind, randomized, crossover trial. Acebutolol decreased supine systolic blood pressure from 186.5 to 162.7 mmHg and diastolic blood pressure from 107.4 to 92.4 mmHg. Hydrochlorothiazide decreased systolic blood pressure from 185.0 to 166.4 and diastolic blood pressure from 107.2 to 96.4. There was no difference between the effects of acebutolol and hydrochlorothiazide on blood pressure during the trial. Both drugs proved to be safe and effective antihypertensive agents, provided the major contraindications for their use were taken into account. Beta-blockade by acebutolol was highly effective in treating mild-moderate arterial hypertension in the elderly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544080
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  • 113
    Electronic Resource
    Electronic Resource
    Acute and long-term antihypertensive effect of bopindolol – A nonselective β-adrenergic blocker with ISA (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 281-285 
    Details
    ISSN: 1432-1041
    Keywords: bopindolol ; metoprolol ; blood pressure ; heart rate ; effect duration ; hypertension ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 14 male hypertensive patients, mean age 53 years first took part in a 3 month, double-blind crossover comparison of 1–2 mg bopindolol, a nonselective β-blocker with ISA, and 100–200 mg metoprolol. Effects on blood pressure and heart rate were followed. One patient dropped out after the initial phase and the remaining 13 patients were followed for 1 year on bopindolol. 8 patients measured blood pressure at home, and in them bopindolol 1 mg o.d. and 8 mg once weekly were compared in a double-blind fashion, for 3 weeks on each regimen. Finally, after 1 year on bopindolol, treatment was withdrawn and blood pressure and heart rate were followed in 10 of the initial patients. Bopindolol in a mean doese of 1.35 mg/day caused a significant reduction in blood in pressure (26/15 mmHg), as did metoprolol (24/13 mmHg) in a mean dose of 144 mg/day. No significant difference in antihypertensive response was observed. Supine and standing heart rate were reduced both during bopindolol and metoprolol treatment. During long-term therapy with bopindolol, satisfactory blood pressure control was maintained up to 1 year in all patients, the average supine blood pressure being reduced from 173/107 to 144/90 mmHg. During treatment with bopindolol 8 mg once weekly, the blood pressure control was satisfactorily maintained over the week and no significant difference was observed in comparison with daily administration (1 mg) of the drug. When active treatment was withdrawn, a gradual increase in blood pressure and heart rate was observed, the pretreatment values being reached 8 weeks after discontinuation of bopindolol therapy. Thus, effective blood pressure control was achieved with bopindolol in patients with mild hypertension. The effect was sustained over 12 months and tolerance was good. The relatively long half-life of the drug made it possible to use it in once weekly regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544081
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  • 114
    Electronic Resource
    Electronic Resource
    Improvement of glucose tolerance in hypertensive diabetic patients treated with guanfacine one year (1985)
    Springer
    European journal of clinical pharmacology 29 (1985), S. 391-393 
    Details
    ISSN: 1432-1041
    Keywords: diabetes mellitus ; hypertension ; guanfacine ; glucose tolerance ; insulin ; side-effects ; coronary risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the present study the effect of 1 year of antihypertensive treatment with guanfacine (g) has been evaluated in 18 hypertensive patients with adult-onset, non-insulin-dependent diabetes mellitus (WHO Type II). The treatment produced a marked improvement in the oral glucose tolerance test; guanfacine significantly decreased serum glucose levels, and affected only slightly the insulin secretion. It is suggested that the effect of g may be mediated via a reduction in catecholamine and/or growth hormone and ACTH secretion. The present results also suggest that treatment with guanfacine may improve individual coronary risk in hypertensive diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613450
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  • 115
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of trimazosin and its effects on blood pressure, renal function and proteinuria during short-term therapy of patients with impaired renal function and hypertension (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 63-68 
    Details
    ISSN: 1432-1041
    Keywords: trimazosin ; proteinuria ; chronic renal insufficiency ; hypertension ; glomerular filtration rate ; renal vascular resistance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics and short-term (10 weeks) effects of trimazosin, an alpha1-adrenoreceptor antagonist, on renal function and blood pressure in patients with moderate chronic renal insufficiency and hypertension, have been studied for the first time. Eight patients in whom the blood pressure was not normalized with a diuretic alone underwent pharmacokinetic studies and assessment of the renal function during a 10-week period of trimazosin therapy. Trimazosin significantly lowered blood pressure (recumbent and upright) without significantly altering renal function. Renal vascular resistance was decreased by 14%. Fractional sodium excretion, proteinuria and laboratory serum tests remained unchanged. Neither body weight nor pulse rate were affected. Moderate renal insufficiency did not modify the pharmacokinetics of the drug. Thus, trimazosin, as second-step antihypertensive agent, appeared to be safe and effective in patients with moderate renal insufficiency and hypertension, without exerting favourable or adverse renal effects during short-term therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00870988
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  • 116
    Electronic Resource
    Electronic Resource
    Antihypertensive effects of bisoprolol during once daily administration in patients with essential hypertension (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 517-521 
    Details
    ISSN: 1432-1041
    Keywords: bisoprolol ; hypertension ; beta-adrenoceptor blocker ; once-a-day administration ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Biosprolol is a new beta1-selective beta-blocking agent with a plasma half-time of 10–12 h and without partial agonist properties. Forty-eight patients with essential hypertension were randomly treated with 5, 10, or 20 mg bisoprolol given once daily for 8 weeks. All measurements were made 24 hours after the last dose. Bisoprolol had antihypertensive and beta-blocking properties both at rest and during exercise. The 20 mg dosage regimen was more effective than that of 5 mg and 10 mg. The drug was well tolerated and all the 48 patients completed the trial.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635886
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  • 117
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    Controlled clinical trial of cadralazine as a second-step drug in the treatment of hypertension (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 135-138 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; cadralazine ; vasodilators ; chlorthalidone ; atenolol ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy of a new long-lasting vasodilator, cadralazine, and the diuretic chlorthalidone have been compared in hypertensive patients receiving concurrent treatment with atenolol. After a 4-week run-in period with atenolol alone 100 mg/day, two groups of 10 patients whose diastolic blood pressure exceeded 100 mm Hg were given for a period of 65 days either cadralazine 15 mg/day or chlorthalidone 25 mg/day, according to a randomized, double-blind, between-patients design. Compared to atenolol alone, both cadralazine and chlorthalidone induced a statistically and clinically significant decrease in blood pressure. The antihypertensive effect did not differ significantly between groups. Good compensation of the atenolol-induced decrease in heart rate was obtained with cadralazine, whereas during atenolol + chlorthalidone treatment at times the standing heart rate was significantly lower than during treatment with atenolol + cadralazine. Side-effects, many of which were already present during atenolol treatment, occurred with a similar frequency in both groups. It is concluded that atenolol + cadralazine and atenolol + chlorthalidone are equally well tolerated, acceptable and effective in the treatment of hypertension, but that further studies are warranted to explore the potential haemodynamic advantages of the cadralazine + atenolol combination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609680
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  • 118
    Electronic Resource
    Electronic Resource
    Treatment of essential hypertension: Changes in blood pressure echocardiography and electrocardiography on three therapeutic regimes (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 119-124 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; cardiac hypertrophy ; echocardiography ; therapeutic regimes ; beta-receptor blockade ; hydralazine ; methyl-dopa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Forty-three patients with essential hypertension were randomly allocated to one of the following treatment regimes; — atenolol, atenolol and hydralazine or methyl dopa. Blood pressure fell into the normal range at 3 months and was similar in all 3 groups. Blood pressure remained controlled over the period of study. M-mode echocardiography was assessed initially, at 3, 6 and 12 months. All groups showed a fall in the measured indices towards the normal range with a significant reduction in left ventricular wall thickness at 3 months in the methyl dopa group and left ventricular mass in the atenolol group alone of 6 months. In conclusion, no one treatment regime appeared to have sustained advantages over another and none of the groups showed any deterioration on echocardiographic criteria during the study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609677
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  • 119
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    Pinacidil, a new vasodilator, in the treatment of mild to moderate essential hypertension (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 347-349 
    Details
    ISSN: 1432-1041
    Keywords: pinacidil ; hypertension ; vasodilation ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty three patients with essential hypertension who were uncontrolled on diuretic and/or β-receptor antagonist therapy were treated additionally with the vasodilator, pinacidil, in an open study. Significant reduction in mean blood pressure was achieved. Supine and erect systolic and diastolic blood pressure fell by 44/25 mmHg and 37/24 mmHg respectively over the study period of 12 weeks. Side-effects such as dizziness, headache, facial flushing and mild oedema were experienced by 10 patients during the study, all of which were mild and transient and did not require withdrawal from pinacidil therapy. Pinacidil is an effective and well tolerated agent in the treatment of essential hypertension.
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    URL: http://dx.doi.org/10.1007/BF00543335
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    Antihypertensive therapy with a single daily dose of acebutolol in essential hypertension, response and ophthalmological assessment in the Japanese (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 709-711 
    Details
    ISSN: 1432-1041
    Keywords: acebutolol ; hypertension ; antinuclear antibody ; practolol syndrome ; ocular examination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty patients with essential hypertension were given 400 mg acebutolol once daily for 24 weeks. In order to study if side effects resembling the “Practolol syndrome” developed, ocular effects were sought and antinuclear antibody (ANA) in blood was assessed before and after treatment. ANA was negative both before and after the study in 17 patients; in one patient ANA was positive, but the titre (1:10) was low and did not change during the study. Acebutolol produced no undesirable effects on cornea, conjunctiva or lens. During acebutolol treatment, tear secretion was reduced but tear lysozyme concentration was not significantly altered. Overall, acebutolol had no undesirable action similar to the practolol-induced syndrome, nor did it cause such common clinical ocular symptoms such as dry or gritty eyes.
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    URL: http://dx.doi.org/10.1007/BF00607921
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    Antihypertensive effects of urapidil and clonidine: A double-blind cross-over study (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 35-39 
    Details
    ISSN: 1432-1041
    Keywords: urapidil ; clonidine ; hypertension ; side-effects ; hypotensive effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of urapidil and clonidine have been studied in a double-blind cross-over trial in 11 hypertensive outpatients with mild to moderate hypertension, at rest and during isometric exercise. Urapidil 30 mg b.i.d. significantly decreased the standing diastolic blood pressure (p〈0.05) and the systolic blood pressure at the end of isometric exercise (p〈0.05). Clonidine 0.075–0.15 mg b.i.d. was more effective in decreasing both systolic and diastolic blood pressure in the supine and standing positions as well as during isometric work (p〈0.05–0.001). Urapidil caused fewer side-effects than clonidine. Overall, in the doses used urapidil had a weaker antihypertensive effect and caused fewer side-effects than clonidine.
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    URL: http://dx.doi.org/10.1007/BF00635705
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    A pharmacokinetic study of prazosin in patients with varying degrees of chronic renal failure (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 333-337 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; renal failure ; hypertension ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic parameters of prazosin (t1/2, tmax, Cmax and AUC have been studied in 18 hypertensive patients with varying degrees of chronic renal failure (serum creatinine ranging from 1.6 to 11.4 mg/dl). An oral dose of 2 mg of prazosin was added to the preexisting antihypertensive medication. The degree of renal impairment did not influence the peak drug concentration, the time to peak or the serum half-life. On the other hand, the hypotensive action after 2 mg prazosin, was more pronounced in patients with severe chronic renal failure. This effect could not be explained by a difference in the pharmacokinetics of prazosin in severe as compared to moderate chronic renal failure or to normal renal function.
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    URL: http://dx.doi.org/10.1007/BF00981133
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    Sustained release verapamil in hypertension. Results from a noninvasive ambulatory blood pressure monitoring and a clinical study (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 255-259 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; hypertension ; sustained-release formulation ; noninvasive ambulatory pressure monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of a new sustained-release matrix formulation of verapamil 200 mg was investigated in a dose-response study in patients with mild to moderate essential hypertension. Noninvasive ambulatory blood pressure measurements were recorded over 24 h in 6 patients with diastolic blood pressure ≥100 mmHg. The patients received sustained-release verapamil 200 mg once daily and twice daily in a randomized order. Each medication period lasted 2 weeks. Verapamil 200 mg twice daily had a better antihypertensive effect than the same dose once daily. After a 6-week placebo period 27 patients with a diastolic blood pressure ≥100 mmHg were included in a double-blind clinical trial. The patients received sustained release verapamil 200 mg once daily and twice daily in a randomized crossover manner. Each medication period lasted 6 weeks, with an intervening 6-week placebo period. A diastolic blood pressure of ≤95 mmHg was achieved in 6 patients with the once-daily regimen and in 14 with the twice-daily regimen. The mean fall in diastolic blood pressure was 4 and 9 mmHg, respectively (p〈0.05). We conclude that sustained-release verapamil 200 mg once daily gives a satisfactory blood pressure response only in a minority of patients, while 200 mg twice daily has a significantly better antihypertensive effect. Both doses were well tolerated.
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    URL: http://dx.doi.org/10.1007/BF00981120
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    Acute systemic and renal haemodynamic effects and long-term antihypertensive action of cadralazine in patients pretreated with β-blockers and diuretics (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 513-518 
    Details
    ISSN: 1432-1041
    Keywords: cadralazine ; hypertension ; haemodynamic effects ; renal blood flow ; glomerular filtration ; renal function ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of the hydralazine-related compound cadralazine (2-{3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl}ethyl carbazate, ISF 2469), were investigated in 16 patients with primary hypertension concurrently treated with β-blockers and diuretics. The protocol included a double-blind placebo controlled haemodynamic evaluation after the first tablet and two 4-week double-blind placebo controlled cross-over periods followed by an open evaluation during 2 months. Cadralazine induced a moderate, prolonged fall in blood pressure that was associated with vasodilatation and slight increases in cardiac output (dye-dilution) and heart rate. Renal plasma flow (PAH) and glomerular filtration rate (51Cr-EDTA) were not significantly influenced, but the filtration fraction was reduced. Plasma concentrations of noradrenaline and adrenaline rose, whereas plasma renin activity was unchanged. The haemodynamic parameters were not correlated with the plasma concentrations of cadralazine. During chronic cadralazine treatment the supine blood pressure was significantly lower than during the double-blind placebo phase (160/93 vs 174/102 mmHg). The compound was generally well tolerated but the body weight increased slightly (1.1 kg), probably because of fluid retention. Several patients who had previously experienced side effects with hydralazine, including one with hydralazine-syndrome, tolerated cadralazine well. This suggests that cadralazine does not cross-react with hydralazine.
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    URL: http://dx.doi.org/10.1007/BF00606622
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    Pharmacokinetics of ketanserin in patients with essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 259-265 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; ketanserin-ol ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketanserin and its main metabolite ketanserin-ol, and the antihypertensive effects of intravenous, single oral and chronic oral (40 mg once daily) administration of ketanserin, have been investigated in a single blind study of 10 patients with uncomplicated mild hypertension. Ketanserin had a terminal half-life of 29.2 h, a plasma clearance of 518 ml/min and a volume of distribution of 18.0 l/kg. Chronic oral intake of 40 mg ketanserin (tablet formulation) gave a peak concentration of unchanged ketanserin of 88 ng/ml after 1.1 h. Its absolute bioavailability was 48%. During chronic therapy the maximal concentration of ketanserin-ol was 208 ng/ml and its half-life of elimination was 35.0 h. As this metabolite can be oxidized back to ketanserin, it contributes to the prolonged half-life of unchanged ketanserin seen during chronic therapy. The blood pressure was reduced by approximately 15% by oral ketanserin. The maximal reduction in blood pressure coincided with the peak concentration of unchanged ketanserin. During chronic therapy with 40 mg once daily blood pressure was reduced over 24 h. The heart rate was slightly reduced and the cardiovascular responses and the plasma noradrenaline concentrations during isometric exercise were only slightly influenced by ketanserin therapy. Thus, unchanged ketanserin has a relatively long half-life during chronic oral therapy and its pharmacokinetics in middle-aged hypertensive patients is similar to that in normal young volunteers.
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    URL: http://dx.doi.org/10.1007/BF00607573
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    Torasemide, a new potent diuretic (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 29-34 
    Details
    ISSN: 1432-1041
    Keywords: torasemide ; hypertension ; diuretic potency ; furosemide ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacodynamic effects of torasemide, a new potent loop diuretic, were compared with those of furosemide in a double blind controlled study in 18 hypertensive patients with oedema of various origins. Given orally for 5 days, torasemide was clinically very effective and well tolerated. On a weight basis, the diuretic, natriuretic and chloruretic effects of torasemide were about 8-times greater than those of furosemide. However, the kaliuretic effect of torasemide was only 3-times greater than that of furosemide, suggesting that torasemide is more potassium sparing than furosemide. Torasemide displayed a rapid onset of action, similar to that of furosemide but had a longer diuretic effect without any rebound phenomenon. Torasemide and furosemide did not effect creatinine clearance or uric acid excretion. Both furosemide and torasemide lowered systolic blood pressure but the effect of torasemide was more marked than that of furosemide. In this group of aged and hypertensive patients with oedema, the pharmacokinetics of torasemide was comparable to that reported in young healthy volunteers, and were similar on the first and fifth days of treatment. The long duration of action and the potassium sparing effect of torasemide compared to furosemide are promising features of this new loop diuretic in the treatment of oedema and hypertension.
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    URL: http://dx.doi.org/10.1007/BF00541464
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    Lisinopril in hypertensive patients with and without renal failure (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 11-16 
    Details
    ISSN: 1432-1041
    Keywords: lisinopril ; hypertension ; converting enzyme inhibition ; serum drug concentratoin ; blood pressure ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Lisinopril (MK521), a lysine analogue of enalaprilic acid, the bioactive metabolite of enalapril, has a longer half-life than enalaprilic acid, and is excreted unchanged in the urine. Its kinetic profile and antihypertensive and hormonal effects have been investigated in an open study in 3 groups each of 6 hypertensive patients, with normal, moderate and severe impairment of renal function. Serum drug level, blood pressure, converting enzyme activity (CEA), plasma renin activity (PRA), aldosterone concentration (PAC), and serum potassium and creatinine were measured during 1 week following a single oral dose and subsequently following 8 daily doses of 5 mg lisinopril. Accumulation of lisinopril was found in the severe renal failure group. CEA was suppressed to less than 10% of its initial value from 4 to 24 h after the initial dose in all three groups, and the suppression was more marked and lasted longer in patients with severe renal failure. An inverse correlation was found in all patients between log serum lisinopril concentration and log CEA. Lisinopril lowered blood pressure in all three groups over 24 h. PRA rose and PAC fell similarly in the groups. Serum potassium increased in the renal failure groups and creatinine remained unchanged in all groups. Thus, when lisinopril 5 mg is given daily to patients with severe renal failure it may accumulate. The high serum lisinopril concentration does not cause an excessive antihypertensive effect. In patients with severe renal failure, adjustment of the dose or the dosing frequency to the degree of renal failure is recommended to avoid administration of doses in excess of those required to achieve adequate inhibition of converting enzyme.
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    URL: http://dx.doi.org/10.1007/BF00609951
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    Effect of sustained-release verapamil therapy on the blood pressure at rest and on the pressor response to isometric exertion in hypertensive patients (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 549-553 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; hypertension ; sustained-release formulation ; handgrip test ; pressor activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a new formulation of verapamil sustained release (SR) 240 mg tablets on resting blood pressure (BP) and on the pressor response to isometric exertion have been examined in a single-blind, placebo-controlled, cross-over study in 12 hypertensive patients (mean age 45 years). SR verapamil and placebo were administered every 12 h for 6 consecutive weeks. At the end of each period of treatment BP and heart rate (HR) were measured at rest and during isometric exercise, performed as a handgrip (HG) test for 3 min at 30% of the maximum voluntary contraction. There was a significant reduction in resting systolic and diastolic BP, with no change in HR. BP and HR at peak exercise were lower after verapamil than after placebo, but the maximal absolute increase did not change during verapamil therapy. The results are compatible with a role of SR verapamil b.d. in reducing resting BP in hypertension, and in lowering very high pressure at the peak of a HG test, without modifying the physiological reactivity of cardiovascular system.
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    URL: http://dx.doi.org/10.1007/BF00615216
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    Renal function and blood pressure in patients treated with cyclosporin a for uveitis (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 601-604 
    Details
    ISSN: 1432-1041
    Keywords: cyclosporin A ; uveitis ; renal function ; creatinine clearance ; hypertension ; corticosteroids ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Renal function has been evaluated in 21 patients treated with cyclosporin A (CyA) for 9 months for idiopathic uveitis. Serum creatinine, which was 82 µmol·l−1 before treatment, was significantly elevated after 1 month (111 µmol·l−1). After 9 months of treatment, and despite a decrease in CyA dosage, the mean plasma creatinine remained elevated at 132 µmol·l−1. Hypertension developed in 6 patients, five of them being concomitantly treated with corticosteroids. In 8 patients serum creatinine 3 months after CyA had been stopped had decreased from 148 to 93 µmol·l−1. Two of those patients remained hypertensive 3 months after CyA treatment had ceased. In patients with idiopathic uveitis CyA induces a reversible increase in serum creatinine. However the reversibility of such a biochemical marker does not preclude a histopathological lesion. Chronic renal damage may be responsible for the persistance of hypertension after cessation of CyA treatment
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    URL: http://dx.doi.org/10.1007/BF00615224
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    Assessment of ‘once daily’ verapamil for the treatment of hypertension using ambulatory, intra-arterial blood pressure recording (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 549-553 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; hypertension ; bicycle exercise ; isometric hand-grip
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A new, slow release formulation of verapamil, “verapamil o.d.” was administered to 12 patients with essential hypertension. Drug administration was started at a dose of 240 mg and increased to 480 mg after 2 weeks of treatment if the cuff blood pressure response was unsatisfactory. The drug reduced the daytime intra-arterial blood pressure significantly from 180.7/106.8 mm Hg to 157.3/89.4 mm Hg. The daytime heart rate fell from 88.1 to 71.8 beats/min. The nighttime blood pressure decreased from 155.7/87.2 mm Hg to 140.5/75.3 mm Hg. The nocturnal heart rate decreased from 62.8 to 57 beats/min. Hourly plots of mean systolic and diastolic pressure showed a significant reduction of systolic pressure for 21 of 24 h and of diastolic pressure for all 24 h following a single morning dose. The drug modified the absolute blood pressure and heart-rate response during both forms of exercise, but did not alter the magnitude or rate of blood pressure change. The tilt-test produced no evidence of postural hypotension. Only one patient experienced any side effects whilst taking the drug. These results indicate good 24-h blood pressure control and reduced exercise blood pressure levels during treatment with this new formulation of verapamil. The reduced frequency of drug administration should improve patient complicance with treatment of hypertension.
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    The efficacy of a transdermal formulation of clonidine in mild to moderate hypertension and its effects on the arterial and venous vasculature of the forearm (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 111-114 
    Details
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; transdermal administration ; baroreflex ; arterial compliance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the efficacy of clonidine hydrochloride administered transdermally once a week for 9 to 15 weeks in 12 patients with mild to moderate hypertension. Clonidine reduced both supine and standing blood pressures on average, but only 8 subjects were responders, i.e. had a decrease in supine diastolic blood pressure to below 90 mm Hg or more than 10% from baseline. Supine heart rate was unchanged, but in the responders the orthostatic increase in heart rate was reduced by clonidine from baseline (p〈0.05). Moreover, in all the patients the change in the orthostatic increase in heart rate was correlated with the change in supine diastolic pressure (p〈0.05). Brachial artery blood flow, forearm arterial compliance, vascular resistance, and venous tone were not affected by clonidine. Thus, transdermal clonidine reduced blood pressure, probably by a baroreflex-mediated effect, but did not affect the vasculature of the forearm.
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    Flosequinan as a third agent for the treatment of hypertension: A placebo controlled, double-blind study (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 203-204 
    Details
    ISSN: 1432-1041
    Keywords: flosequinan ; hypertension ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute and short term antihypertensive effect of flosequinan was determined in 16 hypertensive patients whose blood pressure was inadequately controlled despite treatment with a β-adrenoceptor blocking agent and a diuretic. Erect and supine systolic and diastolic blood pressure was significantly reduced by flosequinan over the treatment period as compared to placebo. Heart rate was unchanged by flosequinan. Adverse effects were limited to mild headache in 3 patients and taste disturbance in 1 patient, possibly due to salivary excretion of the drug. Flosequinan is a potentially useful vasodilator for the treatment of hypertension.
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    Plasma renin activity does not predict the antihypertensive efficacy of chlorthalidone (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 221-226 
    Details
    ISSN: 1432-1041
    Keywords: renin-angiotensin system ; chlorthalidone ; hypertension ; multicentre study ; plasma renin activity ; dose prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It has been established that angiotensin II stimulation may limit the antihypertensive potential of diuretic therapy in some patients. It is less clear, however, whether renin-angiotensin II stimulation is the cause of the flat blood pressure dose-response relationship to diuretics. To investigate this, 75 out-patients with essential hypertension were treated with chlorthalidone 12.5, 25 or 50 mg o.d. for 3 weeks, in a double-blind, placebo controlled cross-over study. Chlorthalidone significantly reduced blood pressure in all the groups, a plateau being reached at 25 mg o.d. Similarly, plasma renin activity was increased by each dose level of chlorthalidone, but it showed a different trend, being increased to a comparable extent at 12.5 mg and 25 mg o.d., and still higher at 50 mg o.d. Thus, greater stimulation of renin was coincident with the levelling of the blood pressure response to chlorthalidone. However no significant correlation was found between interindividual plasma renin activity and change in blood pressure, either in the entire series, or in each treatment subset. The data suggest overall that renin stimulation may influence the characteristic dose-hypotensive response relationship to diuretic agents in antihypertensive therapy, but it is unlikely that measurement of individual plasma renin activity will provide an useful guide to the optimal dose of a diuretic agents.
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    Adrenergic system and carbohydrate metabolism. Effects of beta-receptor blockade on insulin secretion and peripheral insulin sensitivity in normoglycaemic patients (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 273-277 
    Details
    ISSN: 1432-1041
    Keywords: beta-adrenoreceptor blockers ; normoglycaemia ; glucose tolerance ; insulin secretion and -sensitivity ; hypertension ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique. Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment. The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin.
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    The effects of prazosin and propranolol in combination with thiazide diuretics on blood pressure and serum lipids: a multicentre study (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 339-344 
    Details
    ISSN: 1432-1041
    Keywords: prazosin ; propranolol ; hypertension ; antihypertensive effects ; lipid metabolism ; multicentre study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have carried out randomized 12-week multicentre study to compare the effects of prazosin and propranolol on blood pressure and serum lipids in 70 patients with essential hypertension after a 4 week minimum period of treatment with thiazide diuretics. After 12 weeks treatment with prazosin (n=40, 1.5–12.0 mg per day) or propranolol (n=30, 30–120 mg per day) with diuretics there was a significant blood pressure reduction from 165.1/97.9 mmHg to 151.2/90.6 mmHg and from 167/96.5 mmHg to 153/91.9 mmHg, respectively. In the 12th week a significant decrease was noted in triglyceride and in low-density lipoprotein cholesterol (LDL + VLDL-C), but no significant effects were seen in high-density lipoprotein cholesterol (HDL-C) in patients receiving prazosin. On the other hand, a significant decrease in lecithin cholesterol acyltransferase (LCAT) was seen in patients receiving propranolol. Twenty-six of 40 patients receiving prazosin were given an additional 12 weeks of treatment. Twenty-two of 30 patients initially treated with propranolol were switched from propranolol to prazosin after 13 weeks and given prazosin up to the 24th week. At 24 weeks, the blood pressure was 149/93.0 mmHg in the prazosin group and 155/89.2 mmHg in the group which switched from propranolol to prazosin. Triglyceride remained reduced in the prazosin group at the 24th week. In the group which switched from propranolol to prazosin, triglyceride decreased significantly over the next 12 weeks.
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    URL: http://dx.doi.org/10.1007/BF00637627
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    Enalapril and hydrochlorothiazide in hypertensive Africans (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 229-234 
    Details
    ISSN: 1432-1041
    Keywords: enalapril ; hydrochlorothiazide ; hypertension ; side-effects ; Africans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy both of angiotensin converting enzyme (ACE) inhibitors and thiazide diuretics has been claimed to be influenced by plasma renin activity, which declines with age and is low in blacks. In a double-blind, placebo-controlled, double-dummy, randomized, parallel-group preliminary study, the antihypertensive efficacy and tolerability of the ACE inhibitor enalapril (20 mg day−1) and hydrochlorothiazide (50 mg day−1) were evaluated and compared for 4 weeks in 20 African patients with essential hypertension. The two groups had similar baseline clinical features and serum Na+ and K+ levels. Hydrochlorothiazide caused a significant and sustained fall in erect blood pressure with a reflex tachycardia. Enalapril exerted only a modest antihypertensive action, but significantly reduced erect heart rate. Direct comparison of hydrochlorothiazide — and enalapril — induced hypotension suggested a greater fall in subjects on the thiazide. The 95% confidence limits for the thiazide-enalapril difference in antihypertensive action at the end of the study was 39.5 to −7.5 mm Hg systolic and 22.0 to −6.6 mm Hg diastolic. The maximal blood pressure fall after hydrochlorothiazide was positively correlated with age (r=0.50;p〈0.05), whilst that of enalapril was inversely related age to (r=−0.57,p〈0.05). The results are compatible with the notion that ACE inhibitor monotherapy may be less effective than thiazide diuretic treatment in African and black patients with essential hypertension. The findings also support the concept that age and racial factors may influence the response to antihypertensive treatment.
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    URL: http://dx.doi.org/10.1007/BF00558152
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    Verapamil and bendrofluazide in the treatment of hypertension: A controlled study of effectiveness alone and in combination (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 249-253 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; bendrofluazide ; hypertension ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of verapamil and bendrofluazide used singly and in combination were examined in patients with primary hypertension in a patient blind, partly observer blind placebo controlled study of parallel group design; there were ten subjects in each arm of the trial. Verapamil 160 mg twice daily caused supine mean arterial pressure to fall by 21 mm Hg; this reduction was significantly greater (p〈0.05) than that induced by bendrofluazide 5 mg daily which caused a fall of only 10 mm Hg. The addition of verapamil 160 mg twice daily to bendrofluazide 5 mg daily caused a further fall in pressure of 18 mm Hg (p〈0.005), but the reduction in pressure when bendrofluazide was added to verapamil was only 1 mm Hg and not significant. Bendrofluazide therapy caused a fall in plasma potassium concentration and an increase in plasma urate concentration; urinary calcium excretion was reduced. Verapamil caused no detectable biochemical alterations in plasma or urine.
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    24-hour control of blood pressure by once daily doxazosin: a multicentre double-blind comparison with placebo (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 613-618 
    Details
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; adverse effects ; multicentre study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy of the new, once daily, alpha1-adrenoceptor inhibitor, doxazosin, was compared with placebo in 40 patients with mild to moderate hypertension. Following a dose titration the mean final daily doxazosin dose in 20 patients was 13.1 mg. Through-the-day blood pressure control was assessed by frequent measurements during 24 h hospitalisation in the 9 th week of double-blind treatment compared with similar measurements made during a 2 week single-blind placebo run-in. Mean reductions in standing and supine systolic and diastolic blood pressure during doxazosin treatment were statistically significantly greater than during placebo treatment at most hourly time points during the 24 h post-dose period. Twenty-four post-dose the mean falls in standing and supine diastolic blood pressure during doxazosin treatment were statistically significant when compared with placebo. Adverse effects during doxazosin treatment were generally minor and were tolerated or disappeared with continued therapy. No patients were withdrawn from the study due to adverse effects. We conclude that once daily doxazosin provides smooth and effective blood pressure control throughout a 24 h post-dose period.
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    URL: http://dx.doi.org/10.1007/BF00615226
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    Acute calcium entry blockade inhibits the blood pressure but not the hormonal responses to angiotensin II (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 567-573 
    Details
    ISSN: 1432-1041
    Keywords: isradipine ; hypertension ; blood pressure ; calcium entry blockade ; renin angiotensin system ; aldosterone plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of acute calcium entry blockade by isradipine (IS) and placebo (P) on the haemodynamic and humoral responses to angiotensin II (A II) have been compared in two groups of 9 patients with essential hypertension. During 4 sequential periods each of 20 min, an i.v. infusion of A II 0, 2, 4 and 8 ng · kg−1 · min−1 was given before (control) and 30 min after the oral administration either of IS or P. After IS, both the blood pressure and the angiotensin II-induced pressor effect were significantly reduced. Isradipine increased the heart rate and this cardio-acceleration was potentiated by A II. In contrast, when A II was infused in the absence of IS, heart rate tended to decrease. IS stimulated plasma renin activity and reduced plasma aldosterone. However, it did not affect either the inhibition of plasma renin activity or the rise in plasma aldosterone in response to A II. In conclusion, acute calcium entry blockade in patients with essential hypertension reduces the pressor response to A II, but not the A II-induced inhibition of renin and increase in plasma aldosterone.
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    URL: http://dx.doi.org/10.1007/BF00637737
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    Ambulatory blood pressure monitoring during sustained treatment with conventional and extended-release felodipine in mild-to-moderate hypertension (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 555-557 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; hypertension ; ambulatory blood pressure monitoring ; slow-release formulation ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To assess the duration of the antihypertensive effect of the dihydropiridine calcium antagonist felodipine in conventional (C-F) and slow-release (ER-F) formulations, 12 patients with essential hypertension underwent ambulatory blood pressure monitoring (ABPM) at the end of a 2-week treatment period with C-F 5 mg b.d., ER-F 10 mg once daily (o.d.) and placebo. C-F, ER-F and placebo were given in a double-blind 3×3 latin square design 4 times replicated. There was no systematic change in the ABP profile over the three study periods regardless of the treatment. In comparison to placebo, the mean 24-h systolic and diastolic blood pressures showed a significant and similar reduction after both formulations of F. Compared to placebo, C-F and ER-F induced a significant reduction in systolic blood pressure for 15 and 21 h, respectively, and of diastolic blood pressure for 16 and 21 h, respectively. Three patients complained of headache (mild in 2, moderately severe in 1), and two patients of nocturia, with either formulation of F.
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    Cadralazine and chlorthalidone as a second-step drug with atenolol in hypertensive patients: Differences in blood pressure control during exercise (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 145-150 
    Details
    ISSN: 1432-1041
    Keywords: cadralazine ; chlorthalidone ; atenolol ; hypertension ; exercise ; metabolic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The long-term efficacy of a new vasodilator, cadralazine (ISF 2469), and chlorthalidone have been compared in 20 hypertensive patients not adequately controlled by atenolol. After 4 weeks of treatment with atenolol 100 mg once daily, patients whose diastolic blood pressure was 〉95 mmHg were randomly divided into two groups to receive in addition to atenolol, either cadralazine 15 mg once daily or chlorthalidone 25 mg once daily. Both treatments were administered for 6 months. At the end of treatment with atenolol and after 3 and 6 months of combination therapy, blood pressure and heart rate were measured at rest and during bicycle exercise 24 h after the last dose. Compared to atenolol alone, both cadralazine and chlorthalidone caused a significant and similar reduction in resting blood pressure. Both groups showed an increase in diastolic blood pressure during exercise while receiving atenolol alone. The addition of chlorthalidone did not modify the pressor response to exercise, whereas patients taking cadralazine had a decrease in exercise diastolic blood pressure, which was fully evident after 6 months of therapy. The reduction in exercise diastolic blood pressure induced by cadralazine was proportional to the increase in exercise heart rate, suggesting a fall in peripheral vascular resistance. Chlorthalidone caused a significant increase in serum glucose and uric acid and a decrease in K+, whereas no change was observed during cadralazine It is concluded that cadralazine given once a day with atenolol has the same efficacy in controlling blood pressure at rest as the combination of atenolol and chlorthalidone, and in addition it improves the pressor response to dynamic exercise and does not cause unwanted metabolic effects.
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    Acute haemodynamic and humoral responses to felodipine and metoprolol in mild hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 71-75 
    Details
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; hypertension ; aldosterone ; angiotensin ; cardiac output ; catecholamines ; pulmonary vascular resistance ; renin ; systemic vascular resistance ; haemodynamic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Oral administration of felodipine to 10 patients with mild essential hypertension acutely reduced systemic vascular resistance (SVR) by 40% after 30 min. The change in SVR was significantly related to age (r=−0.74). The reduction in the intraarterially measured brachial artery pressure was limited to 15/13 mmHg, due to a rise in cardiac output (CO). The tachycardia was sustained for 90 min, as was an elevation of plasma noradrenaline. There was a transient increase in stroke volume, associated with a reduction in pulmonary capillary wedge pressure, which was at least partly due to a reduced intravascular volume. In contrast to SVR, pulmonary vascular resistance was not affected by felodipine. Addition of intravascular metoprolol after 90 min decreased HR and CO and augmented SVR. The felodipine-induced rise in plasma renin activity (PRA) of 100% was completely reversed by metoprolol. Plasma angiotensin II (PA II) rose by 15% during felodipine, whereas plasma aldosterone concentration (PAC) was not affected. Thus, actuely administered felodipine was a potent dilator of systemic but not of pulmonary arterioles, it stimulated the sympathetic nervous system, and reduced left ventricular filling pressure. The rise in plasma renin did not result in a higher plasma aldosterone level, due partly to reduced generation of angiotensin II.
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    Effect of nicardipine on insulin secretion, glucose and lipid metabolism in hypertensive, non-insulin dependent diabetics (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 1-4 
    Details
    ISSN: 1432-1041
    Keywords: nicardipine ; insulin ; glucose ; diabetes ; hypertension ; metabolic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Certain acute and chronic metabolic effects of nicardipine have been studied in 20 patients with non-insulin dependent diabetes (NIDD). An intravenous glucose tolerance test (i.v. GTT, glucose 0.33 g/kg as a bolus) and the corresponding insulin response were assessed at the end of a 4 week placebo period, after the first dose and on administration for 12 weeks of nicardipine 20 mg t.i.d. The glucose and insulin responses to the i.v. GTT, evaluated as incremental AUCs, did not change significantly (glucose 30.5 mg/dl·90 min on placebo, 33.1 mg/dl·90 min acutely and 31.4 mg/dl·90 min on chronic administration of nicardipine; insulin 2.08 µU/ml·90 min on placebo, 1.87 µU/ml·90 min acutely and 1.93 µU/ml·90 min after chronic nicardipine). Glucose removal rate (KG) following the i.v. GTT was 0.73%/min on placebo 0.75%/min on acute administration and 0.8%. min−1 with chronic nicardipine. Active treatment produced a significant reduction of blood pressure (from 187/96 mm Hg on placebo to 166/89 mm Hg acutely and 152/83 mm Hg after 12 weeks of nicardipine treatment). It is concluded that the calcium antagonist nicardipine was an effective antihypertensive drug, and that it did not cause deterioration of metabolic control in hypertensive patients with NIDD.
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    Is captopril effective in controlling blood pressure when administered once daily? An assessment using 24-h ambulatory blood pressure monitoring (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 11-15 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; once-daily administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twelve patients with essential hypertension receiving captopril monotherapy or captopril in conjunction with a diuretic had their 24-h blood pressure profiles monitored using an automatic, non-invasive ambulatory method. The study examined the efficacy of once a day versus twice a day administration of the ACE inhibitor in controlling blood pressure. Six untreated subjects with borderline hypertension were also studied using the same monitoring equipment and with the same frequency, to act as controls because of the possibility of repeated use of the device causing a ‘familiarisation’ effect. The results obtained indicated that if anything, the once daily dosing produced marginally better blood pressure values. The amplitude of the diurnal blood pressure variation was reduced on a ‘second-wearing’ of the monitoring equipment suggesting some degree of familiarisation with the apparatus.
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    Effect of carteolol on renal function in healthy subjects and patients with hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 83-86 
    Details
    ISSN: 1432-1041
    Keywords: carteolol ; hypertension ; chronic renal failure ; renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of short- and long-term administration of carteolol on renal function has been examined in healthy subjects and in hypertensive patients with or without renal failure. In healthy subjects neither a single dose of 10 mg carteolol nor continuous administration of 20 mg/day for 7 days had any effect on creatinine clearance and renal blood flow. In all subjects the clearance rate of carteolol was about 400 ml/min and its fractional excretion of carteolol exceeded 300%, suggesting that the drug is secreted actively from renal tubules. Twenty-three hypertensive patients with or without renal dysfunction were given carteolol 10 to 20 mg/day for more than 50 weeks in addition to their standard antihypertensive regimens, which were left changed. Laboratory results were compared with the mean values of 50 weeks before and after the addition of carteolol, and none, including plasma creatinine, blood urea nitrogen and electrolytes, were significantly changed. Neither the estimated glomerular filtration rate nor the effect of the drug on blood pressure changed significantly during this prolonged treatment. It is concluded that carteolol had no effect on renal function in healthy subjects and in hypertensive patients with or without renal failure.
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    Cardiovascular regulation and lipoprotein profile during administration of co-dergocrine in essential hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 119-125 
    Details
    ISSN: 1432-1041
    Keywords: co-dergocrine ; hypertension ; presynaptic dopamine2-receptors ; norepinephrine ; haemodynamic effects ; side-effects ; renin-angiotensin-aldosterone system ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-dergocrine has recently been demonstrated acutely to lower plasma norepinephrine (NE) and blood pressure (BP) in patients with essential hypertension, and similar results have been obtained during chronic administration of co-dergocrine to healthy men. The present study investigated the effect of 3 weeks of treatment with co-dergocrine 4 mg/day on BP, plasma catecholamines, certain other BP-regulating factors and serum lipoproteins in patients with essential hypertension. Compared to placebo conditions, co-dergocrine decreased supine BP and heart rate by −7% and the upright plasma NE level by −24%. Supine plasma NE also fell (−24%). Total cholesterol and the LDL + VLDL-cholesterol lipoprotein fraction were lowered by −6%. No significant change was observed in plasma renin activity, angiotensin II, aldosterone and epinephrine levels, whole blood and plasma volume, exchangeable sodium, and the cardiovascular responsiveness to NE, angiotensin II and isoproterenol. The findings suggest that in patients with essential hypertension, chronic treatment with co-dergocrine may slightly decrease sympathetic outflow and, at least in the short-term, lower the potentially atherogenic serum LDL + VLDL − cholesterol fraction.
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    URL: http://dx.doi.org/10.1007/BF00609182
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    Reversal by the selective D-2 dopamine receptor blocker sulpiride of the hypotensive effect of co-dergocrine in elderly hypertensives (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 519-521 
    Details
    ISSN: 1432-1041
    Keywords: co-dergocrine ; sulpiride ; hypertension ; DA-2 receptors ; dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The aim of the study was to define the role of peripheral dopaminergic mechanisms in the regulation of blood pressure. The data suggest that the hypotensive effect of the dopaminergic agonist co-dergocrine in elderly hypertensive patients is mediated by interaction with peripheral DA-2 receptors, since it was reversed by the selective antagonist sulpiride in a dose that does not significantly cross the blood brain barrier. The findings suggest the possible therapeutic use of dopamine DA-2 agonists in elderly hypertensive patients.
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    Antihypertensive and hypouricaemic effects of nitrendipine in chronic renal failure (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 223-227 
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    ISSN: 1432-1041
    Keywords: nitrendipine ; renal failure ; hypertension ; uric acid excretion ; metabolic effects ; cardiovascular risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the potential therapeutic value of calcium antagonists in hypertension associated with impaired renal function, blood pressure (BP), certain regulatory factors, and metabolic correlates of cardiovascular risk have been assessed in 15 patients with mild to marked chronic renal failure before and after 6 weeks of therapy with nitrendipine. Compared to placebo, nitrendipine (mean final dose 55 mg/day) decreased supine BP from 173/102 to 146/81 mm Hg and upright BP from 170/105 to 145/86 mm Hg. Heart rate, body weight (+0.8 kg) and exchangeable sodium (+176 mmol, not significant) were minimally increased, and plasma and whole blood volume, plasma angiotensin II and creatinine concentrations, and urinary electrolyte and creatinine excretion were not significantly changed. Nitrendipine increased uric acid excretion and lowered plasma uric acid by 24%; glucose, insulin, serum total lipids, and lipoprotein fractions were unchanged.
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    Responses of glomerular filtration, renal blood flow and salt-water handling to acute cardioselective and non-selective β-adrenoceptor blockade in essential hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 343-345 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; pindolol ; renal haemodynamics ; salt-water handling ; hypertension ; beta-adrenoceptor blockade ; ISA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects on renal hemodynamics and salt-water handling of equipotent doses of the cardioselective β-blocker metoprolol (M, 100 mg) and of the non-selective (intrinsic sympathetic activity) β-antagonist pindolol (P, 10 mg) were compared in 30 WHO Grade 1–2 hypertensive men. M lowered pulse rate more than P. Systolic pressure was equally reduced by both agents, and diastolic and mean pressures were decreased only after P. Glomerular filtration rate was not significantly altered by either antagonist, and renal blood flow decreased by approximately 11% both after M and P. Renal vascular resistance was unchanged after P, and was increased by 10% after M. It is concluded that, like the effects on central haemodynamics, ISA is more important in the renal response to β-adrenoceptor blockade than is β-receptor selectivity.
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    Long-term effect of pindolol on lipids and lipoproteins in men with newly diagnosed hypertension (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 347-350 
    Details
    ISSN: 1432-1041
    Keywords: pindolol ; hypertension ; hyperlipidaemia ; chronic treatment ; cholesterol ; HDL ; LDL ; triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This is the first long-term study of pindolol in a population-based sample of men with newly diagnosed hypertension. Eighty-two patients, with a diastolic pressure of 100 mm Hg or more, were identified after screening 6000 men. Many patients were overweight. 82 population controls, matched by sex, age and body mass index, were also recruited. Fourty-eight per cent of the patients and 25% of the controls had a family history of hypertension. Serum triglyceride and urate values were higher in patients than controls at the baseline investigation. Seventy-four patients were followed for 1 year. The dose of pindolol averaged 7.7 mg once daily after 1 year. The diastolic blood pressure was reduced by 13.4 mm Hg. The target pressure of 95 mm Hg or less was achieved in 89% of the patients. The HDL-cholesterol concentration was normal and did not change, whereas the LDL-cholesterol concentration decreased by 0.15 mmol · l−1 during treatment. The total triglyceride values increased transiently up to 6 months, but no significant increase was seen after one year. It is concluded that pindolol had no adverse effect on serum cholesterol and its HDL- and LDL-fractions during 1 year of treatment.
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    Antihypertensive effect of slow-release nicardipine. A placebo-controlled cross-over study (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 439-442 
    Details
    ISSN: 1432-1041
    Keywords: calcium antagonists ; nicardipine ; hypertension ; placebo effect ; slow-release preparation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The magnitude and duration of the anti-hypertensive effect of slow-release nicardipine (SR-Nicardipine) have been compared with placebo in 36 uncomplicated essential hypertensives (diastolic BP 95 to 115 mm Hg after 1-month placebo washout). According to a double-blind, randomized, cross-over design they received SR-Nicardipine 40 mg b.d. and placebo for 1 month. At the end of each treatment period, blood pressure and heart rate were measured 12 h after the evening dose and 1, 2, 3 and 4 h after the morning dose. SR-Nicardipine significantly reduced systolic (SBP) and diastolic (DBP) blood pressure at each time after dosing. The absolute decrements peaked 4 h after dosing (−18.3 and −11.7 mm Hg, respectively) and more than 90% of the peak effect persisted 12 h after dosing, both for SBP and DBP. The heart rate was slightly increased by SR-Nicardipine. Adverse effects monitored with a check-list occurred in 31% of patients during SR-Nicardipine treatment and in 28% on placebo. Thus, SR-Nicardipine 40 mg b.d. has a maintained and significant antihypertensive effect lasting up to 12 h in essential hypertension.
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    Dependent oedema and attenuation of postural vasoconstriction associated with nifedipine therapy for hypertension in diabetic patients (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 333-335 
    Details
    ISSN: 1432-1041
    Keywords: diabetes mellitus ; nifedipine ; hypertension ; oedema ; vasodilator ; blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We studied the incidence of oedema 2 weeks following initation of nifedipine therapy for hypertension in a group of 10 diabetic subjects, and also measured skin blood flow (SBF) with a laser Doppler flowmeter, before and after lowering the foot. SBF with the foot horizontal increased after nifedipine from 0.31V (arbitrary units of flow) to 0.51V (NS). The postural fall in blood flow in dependency was significantly attenuated by nifedipine from 64.4 to 24.0%. Five patients developed ankle oedema. Results were similar in a small group of non-diabetic subjects starting nifedipine. The attenuation of reflex postural vasoconstriction is therefore likely to contribute to development of the oedema associated with starting nifedipine therapy, which should be monitored carefully in diabetic patients.
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    Comparative haemodynamic effects of ketanserin and ritanserin in the proximal and distal upper limb circulations of hypertensive patients (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 215-220 
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    ISSN: 1432-1041
    Keywords: ketanserin ; ritanserin ; hypertension ; haemodynamics ; alpha1-adrenoceptor blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of ketanserin (40 mg p.o.) on blood pressure and brachial haemodynamics (brachial artery diameter, brachial blood velocity and blood flow) have been compared in a double-blind study with those of ritanserin (10 mg p.o.) and placebo. Haemodynamic parameters were measured before and 1 h after treatment. Patients with mild to moderate essential hypertension participated in this study, 6 each on ketanserin, ritanserin and placebo. Placebo significantly reduced heart rate and did not modify the other parameters. Compared to placebo, ketanserin significantly reduced systolic and diastolic blood pressure, increased brachial blood velocity and flow, and decreased forearm vascular resistance. Compared to placebo, ritanserin slightly decreased blood pressure and slightly increased blood flow, but neither effect was significant. When blood circulation to the hand was excluded, neither ketanserin nor ritanserin modified the proximal arterial resistance or blood flow. It is concluded that the actions of ketanserin and ritanserin essentially occurred in the distal part of the upper limb, and alpha1-receptor blockade is probably involved.
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    Bromocriptine in the treatment of hypertension (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 141-144 
    Details
    ISSN: 1432-1041
    Keywords: bromocriptine ; hypertension ; plasma prolactin ; double-blind study ; placebo ; plasma noradrenaline ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The efficacy of bromocriptine in the treatment of hypertension was assessed in a double-blind placebo controlled cross-over study preceded by a dose titration phase. A diuretic and/or a beta-blocker were administered concomitantly in constant dosage to 11 of the 20 patients who received bromocriptine. A wide range of doses of bromocriptine was tolerated. Side-effects of vomiting and postural hypertension did not occur, possibly due to the gradual increase in the administered doses. Plasma prolactin was not raised in this population of hypertensives. In the dose titration phase (n=20), a small fall in diastolic but not in systolic blood pressure occurred with bromocriptine, but only with the patient standing and after exercise. In the double-blind phase (n=9), there was no significant difference in blood pressure between the bromocriptine and placebo treatments. It is concluded that bromocriptine was not effective in lowering blood pressure in the present patients with essential hypertension.
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    Bopindolol versus metoprolol in hypertension (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 379-380 
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    ISSN: 1432-1041
    Keywords: bopindolol ; metoprolol ; hypertension ; blood pressure reduction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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    URL: http://dx.doi.org/10.1007/BF00981143
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    Changes in haemodynamics and body fluid volume due to enalapril in patients with essential hypertension on chronic diuretic therapy (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 381-385 
    Details
    ISSN: 1432-1041
    Keywords: enalapril ; hypertension ; converting enzyme inhibition ; chlorthalidone ; sodium depletion ; blood pressure output ; extracellular fluid volume ; renin ; aldosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment, the effect of 2 weeks of additional therapy with the converting enzyme inhibitor (CEI) enalapril on blood pressure and body fluid volumes has been evaluated. The objective was to examine the influence of a diuretic-stimulated renin-angiotensin-aldosterone system (RAAS) on haemodynamics and body fluid volume. Mean arterial pressure (MAP −21%), total peripheral resistance index (TPRI −22%) and plasma aldosterone concentration (PAC −39%) were decreased, and plasma renin activity (PRA 660%) was increased. The average heart rate (HR), cardiac index (CI), plasma volume (PV), blood volume (BV), extracellular fluid volume (ECFV) and body weight (BW) remained unchanged. A negative correlation was found between the per cent changes in ECFV and PAC. Thus, body fluid volumes during chronic diuretic treatment are well preserved even when the RAAS with its sodium retaining properties is suppressed by CEI. Possible mechanisms are a volume (not angiotensin II) — dependent stimulation of aldosterone and a fall in blood pressure.
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    URL: http://dx.doi.org/10.1007/BF00613510
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    The effect of nisoldipine on renal function in the long-term treatment of hypertension in patients with and without renal impairment (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 437-441 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; renal function/-impairment ; calcium antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of nisoldipine on renal function after 6 weeks treatment was investigated in hypertensive patients with and without renal impairment. Nisoldipine was well tolerated and an effective antihypertensive agent when administered over a period of 6 weeks. There were no significant changes in glomerular filtration, cardiac output, plasma renin activity or serum biochemistry during nisoldipine administration. Effective renal plasma flow was unaffected by treatment in the patients with normal renal function, but in the patients with renal insufficiency, the value decreased by a mean of 12%. Nisoldipine had no major untoward effects on renal function after 6 weeks administration, but minor changes in renal haemodynamics in the patients with renal insufficiency would suggest that careful monitoring of renal function is indicated in such patients.
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    URL: http://dx.doi.org/10.1007/BF00558120
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    Once daily nisoldipine in hypertension: cuff and ambulatory intra-arterial blood pressure (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 551-554 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; hypertension ; ambulatory monitoring ; cuff blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cuff blood pressure data has suggested that the calcium channel antagonist nisoldipine has full twenty four hour efficacy. To test this, 24 h ambulatory intra-arterial blood pressure monitoring was performed on 18 untreated hypertensive subjects (12 men, 6 women) (cuff blood pressure 〉150/95 mm Hg) before and after chronic treatment with 10–20 mg oral nisoldipine taken daily at 08.00 h. Twelve patients completed the study, six being withdrawn, four because of side-effects. After baseline intra-arterial monitoring patients were started on 10 mg nisoldipine daily. Response was assessed by cuff pressures taken 24 h after dosing at fortnightly intervals, and if not controlled (〈150/95 or at least 10 mm Hg reduction in diastolic BP) the dose was increased to 20 mg. All patients received at least six weeks' therapy before the second intra-arterial blood pressure monitoring. There was a slight but insignificant reduction in mean daytime heart rate of 3 beats·min−1. Mean significant reduction in daytime systolic and diastolic BP was 19 mm Hg and 13 mm Hg respectively but there was no significant mean night-time reduction. By comparison 8 out of 12 patients were apparently controlled more than 24 h post dose according to cuff pressures. This study suggests that this formulation of nisoldipine does not control blood pressure over a full 24-h period, and emphasises the importance of 24 h ambulatory monitoring in assessing the efficacy of once-daily antihypertensive agents.
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    URL: http://dx.doi.org/10.1007/BF00562542
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    Human renovascular effects of dopexamine hydrochloride: A novel agonist of peripheral dopamine and beta2-adreno-receptors (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 1-4 
    Details
    ISSN: 1432-1041
    Keywords: dopexamine ; hypertension ; renal blood flow ; cardiac output
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of dopexamine on the renal circulation have been examined to show whether any augmentation of renal blood flow (RBF) was secondary to the effect of the drug on cardiac output (CO) or whether it had any additional direct renal vasodilator activity. Eight male patients with mild to moderate hypertension, who were undergoing renal vein catheterization for renin estimation, were studied. Dose related increments in RBF (baseline (B)=504 ml·min−1; after treatment (D)=605 ml·min−1), CO (B=5.9 l·min−1; D=6.7 l·min−1), heart rate (B=77 beats/min; D=100 beats/min) and systolic blood pressure (B=143 mmHg; D=166 mmHg) were observed on administration of dopexamine 3 µg·kg−1·min−1, with insignificant changes in diastolic blood pressure (B=84.4 mmHg; D=90 mmHg) and total peripheral resistance (B=17.85; D=17.25 Units). There was a slight but significant reduction in renal vascular resistance (B=20.59, D=18.75). The ratio of RBF to CO (%) confirmed that the increase in RBF due to dopexamine hydrochloride was greater that attributable to the increase in CO or perfusion pressure alone (RBF/CO B=8.5%, D=9%), consistent with selective renal vasodilation. The fall in renin activity and lack of systemic vasodilatation suggest that this was a DA1-receptor mediated effect.
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    URL: http://dx.doi.org/10.1007/BF00609949
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    Effects of bisoprolol on blood pressure, serum lipids and HDL-cholesterol in essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 77-80 
    Details
    ISSN: 1432-1041
    Keywords: hypertension ; bisoprolol ; beta1-adrenoceptor blocker ; serum lipoproteins ; HDL-cholesterol ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Fifty patients with essential hypertension WHO Grades I–II have been treated for 3 months with bisoprolol, a new selective betablocker, in doses up to 40 mg once daily. Forty-three patients reached the preset target diastolic blood pressure of ≤ 90 mmHg on a mean daily dose of 16.8 mg bisoprolol. There was no effect on serum lipids and HDL-cholesterol during the study. The side-effects were mild and were those usually associated with beta-blocking therapy.
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    URL: http://dx.doi.org/10.1007/BF00609961
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    Pharmacodynamics and pharmacokinetics of urapidil in hypertensive patients: A crossover study comparing infusion with an infusion-capsule combination (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 61-65 
    Details
    ISSN: 1432-1041
    Keywords: urapidil ; hypertension ; alpha-adrenoceptor blocker ; antihypertensive agent ; pharmacodynamics ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and haemodynamic effects of infused urapidil and an infusion-capsule combination were followed to study the correlation between the serum urapidil level and the blood pressure. Prior to urapidil administration, basal blood pressure and heart rate were measured for 16 h in 12 male hypertensive patients. Six patients received infusions lasting for 4 h of urapidil 10, 2.5 and 5 mg/h. Six patients were infused with urapidil 10 mg/h for 4 h and 2 h after the end of the infusion each took a 60-mg capsule. After a 5 day washout period the procedures were crossed over. A maximum serum urapidil level of 625±232 ng/ml was achieved at the end of the 10 mg/h infusion, when the fall in blood pressure was 37/21 mmHg. During the 2.5 and 5 mg/h infusions the serum urapidil level was 330 and 420 ng/ml, respectively, and the corresponding decreases in blood pressure were 28/16 mmHg and 31/8 mmHg. Although the urapidil concentration 1 hour after beginning the infusion was only 184±89 ng/ml a near maximal blood pressure decrease had already occurred 33±9/20±8 mmHg, whereas, 1 h after the end of the infusion the reduction in blood pressure was only 10±12/3±8 mm, with a urapidil concentration of 358±120 ng/ml. During the plateau phases of both the infusion and infusion-capsule treatments the falls in blood pressure followed the serum urapidil levels. Only in the initial rising and final falling phases of the treatments were the pharmacodynamics and pharmacokinetics of urapidil not correlated.
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    URL: http://dx.doi.org/10.1007/BF00609958
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    Acute natriuretic effect of nifedipine in hypertensive patients and normotensive controls – a proximal tubular effect? (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 121-126 
    Details
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; renal function ; proximal tubule effect ; uric acid ; calcium blockade ; sodium excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute effects of buccal nifedipine 20 mg on blood pressure, renal haemodynamics and electrolyte excretion were compared in 16 untreated patients (HT) with uncomplicated arterial hypertension (WHO I-II), 11 normotensives (NT) and 6 normotensives given a placebo. Nifedipine caused a significant fall in the systolic and diastolic blood pressures (BP) of 25.7±12/26.5±10 mmHg in the hypertensives, and a minor but significant fall in diastolic BP in the normotensives. Renal vascular resistance fell significantly and renal plasma flow was increased non-significantly in the hypertensives. No changes in these parameters were seen in NT. Glomerular filtration rate remained constant in all groups, also in HT despite the marked haemodynamic changes. Natriuresis was significantly increased to the same degree in the HT and NT groups, in spite of their different haemodynamic responses. Uric acid excretion showed a parallel acute increase in both groups. The significant and close relationship between the acute changes in the excretion of sodium and uric acid provides evidence for a proximal tubular natriuretic effect of nifedipine.
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    Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 335-338 
    Details
    ISSN: 1432-1041
    Keywords: chlorthalidone ; magnesium depletion ; hypertension ; adverse effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K+ or Mg++. In the BB-group there was a statistically significant trend towards retention of Mg++ in a loading test, but the effect was clinically marginal. BB + CTD reduced serum K+ and Mg++ and caused significant Mg++ depletion, as shown by the Mg++ loading test. All the effects were highly significant and were clinically important. The metabolic perturbations due to CTD are potentially dangerous and make this drug unattractive as ‘first choice’ treatment for hypertension.
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    Calcium movements during each heart beat (1989)
    Springer
    Molecular and cellular biochemistry 89 (1989), S. 103-108 
    Details
    ISSN: 1573-4919
    Keywords: heart ; relaxation ; calcium ; sodium-calcium exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Transsarcolemmal calcium movements are closely related to force generation in the heart. It is important to understand the transport pathways that control these movements of calcium across the sarcolemmal membrane. In the normal, beating heart, sodium-calcium exchange appears to be an important mechanism for the extrusion of calcium from the cell. The kinetics of this exchange are dependent upon the characteristics of the cell action potential. Calcium efflux via sodium-calcium exchange may be sufficient to balance calcium entry through calcium channels during the action potential.
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    URL: http://dx.doi.org/10.1007/BF00220760
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    Sodium-calcium exchange in mammalian heart: current-voltage relation and intracellular calcium concentration (1989)
    Springer
    Molecular and cellular biochemistry 89 (1989), S. 97-102 
    Details
    ISSN: 1573-4919
    Keywords: calcium ; sodium ; fura-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Membrane currents and changes in intracellular calcium ion concentration ([Ca2+]i) have been recorded that can be attributed to the operation of an electrogenic, voltage-dependent sodium-calcium (Na-Ca) exchanger in mammalian heart cells. Single guinea-pig ventricular myocytes under voltage clamp were perfused internally with the fluorescent Ca2+-indicator, fura-2, and changes in [Ca2+]i and membrane current that resulted from Na-Ca exchange were isolated through the use of various organic channel blockers (verapamil, TTX), impermeant ions (Cs+, Ni2+), and inhibitors of sarcoplasmic reticulum (ryanodine). The I-V relation of Na-Ca exchange was obtained from the Ni2+-sensitive current elicited by ramp repolarization from +90 mV to −80 mV. Ramps were sufficiently rapid that little change in [Ca2+]i occured during the ramp. The (constant) [Ca2+]i during the ramp was varied over the range 100 nM to 1000 nM by varying the amplitude and duration of a pre-pulse to the ramp. The reversal potential of the Ni2+-sensitive ramp current varied linearly with 1n([Ca2+])i. The I-V relations at different [Ca2+]i over the range −60 mV to +140 mV were in reasonable accord with the predictions of a simple, simultaneous scheme of Na-Ca exchange, on the basis that only [Ca2+]i had changed. The relationship between [Ca2+]i and current at a constant membrane voltage was also in accord with this scheme. We suggest that Ca2+-fluxes through the exchanger during the cardiac action potential can be understood quantitatively by considering the binding of Ca2+ to the exchanger during the [Ca2+]i-transient and the effects of membrane voltage on the exchanger.
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    URL: http://dx.doi.org/10.1007/BF00220759
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    Appraisal of the physiological relevance of two hypotheses for the mechanism of calcium release from the mammalian cardiac sarcoplasmic reticulum: calcium-induced release versus charge-coupled release (1989)
    Springer
    Molecular and cellular biochemistry 89 (1989), S. 135-140 
    Details
    ISSN: 1573-4919
    Keywords: calcium ; heart ; sarcoplasmic reticulum ; excitation-contraction coupling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Recent studies correlating the calcium current with, respectively, the clamp-imposed voltage and the calcium current in intact isolated mammalian cardiac myocytes are reviewed. The major findings are the following: [1] With the exception of one group, all investigators agree that a calcium transient is never observed in the absence of a calcium current. In addition, there is a good correlation between voltage dependence of the calcium current and that of the calcium transient, although this correlation may vary among the cardiac tissues from different animal species. [2] Repolarization clamp pulses from highly positive potentials produce a ‘tail current’ which is associated with a ‘tail calcium transient’. [3] The calcium transient is inhibited when the calcium current is blocked by calcium deprivation or substitution, or by the addition of calcium current antagonists, despite the fact that sarcoplasmic reticulum still contains calcium that can be released by caffeine (with inhibition of this release by ryanodine). These three findings are strongly in favor of a calcium-induced release of calcium and against the hypothesis of charge-movement-coupled release of calcium from the sarcoplasmic reticulum. [4] The only finding that would be more in favor of the latter hypothesis (although till reconciliable with the former) is that repolarization occurring before the rapid rise of calcium transient is complete curtails the calcium transient. Thus, the possibility that charge movement might somehow regulate calcium-induced release of calcium cannot be excluded.
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    The effect of acidosis on excitation-contraction coupling in isolated ferret heart muscle (1989)
    Springer
    Molecular and cellular biochemistry 89 (1989), S. 169-173 
    Details
    ISSN: 1573-4919
    Keywords: pH ; calcium ; heart muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The contractile response to acidosis is the final product of a number of different changes in the excitation-contraction coupling pathway: (i) Cai increases and subsequently decreases during acidosis; (ii) the action potential becomes longer; (iii) the sensitivity of the contractile proteins to Ca2+ decreases. The increase of Cai and the lengthening of the action potential may help to maintain contractile function, although this advantage may be offset if spontaneous Ca2− release from the s.r. occurs, secondary to the increase of Cai. The recovery of force shown in figure 1 occurs at a time when the calcium transient is decreasing, and therefore represents an increasing sensitivity of the contractile proteins to Cai, probably due to a recovery of intracellular pH(6), although it is also possible that a disappearance of spontaneous Ca2+ releases from the s.r. may be contributing [2].
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    Membrane transport and disease (1989)
    Springer
    Molecular and cellular biochemistry 91 (1989), S. 3-11 
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    ISSN: 1573-4919
    Keywords: calcium ATPase ; glucose transport ; herpes virus ; hypertension ; leaks ; pore-formation ; sodium channels ; stress ; toxins ; transport ; viruses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Four situations in which membrane transport is altered by disease are discussed: (a) non-specific leaks induced by poreforming agents; (b) glucose transport and cellular stress; (c) Ca+-ATPase and hypertension; (d) Na− channels and HSV infection.
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    The interaction between calcium and the activation of Na+, K+-ATPase by noradrenaline (1985)
    Springer
    Molecular and cellular biochemistry 66 (1985), S. 111-116 
    Details
    ISSN: 1573-4919
    Keywords: Adenosine triphosphatase ; Na+ ; K+ ; catecholamines ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary The interaction of noradrenaline, various cation chelators and calcium on Na+, K+-ATPase from rat cerebral cortex plasma membranes was studied. It was shown that chelation of inhibitory cations by EGTA, EDTA and dipyridyl activated Na+, K+-ATPase to the same extent as noradrenaline but at higher concentrations; increasing concentrations of EGTA depressed the activation by noradrenaline; calcium in the form of a calcium-EGTA buffer depressed Na+, K+-ATPase at physiological concentrations; the inhibition of Na+, K+-ATPase by calcium is dependent on the magnesium concentration in the assay and the inhibition by calcium was partially reversed by noradrenaline.
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    Cation-dependent gonadotropin releasing hormone activation of guanylate cyclase (1985)
    Springer
    Molecular and cellular biochemistry 66 (1985), S. 145-149 
    Details
    ISSN: 1573-4919
    Keywords: calcium ; cyclic GMP ; gonadotropin releasing hormone ; guanylate cyclase ; manganese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Gonadotropin releasing hormone enhanced guanylate cyclase [E.C.4.6.1.2] two- to threefold in pituitary, testis, liver and kidney. Dose response relationships revealed that at a concentration of 1 nanomolar, gonadotropin releasing hormone caused a maximal augmentation of guanylate cyclase activity and that increasing its concentration to the millimolar range caused no further enhancement of this enzyme. There was an absolute cation requirement for gonadotropin releasing hormone's enhancement of guanylate cyclase activity as there was no increase without any cation present. Gonadotropin releasing hormone could increase guanylate cyclase activity with either calcium or manganese in the incubation medium but more augmentation was observed with manganese. The data in this investigation suggest that guanylate cyclase may play a role in the mechanism of action of gonadotropin releasing hormone.
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    Regulation of calcium handling by rat parotid acinar cells (1988)
    Springer
    Molecular and cellular biochemistry 82 (1988), S. 67-73 
    Details
    ISSN: 1573-4919
    Keywords: neurotransmitter control ; secretion ; exocrine ; salivary gland ; calcium ; ATP-dependent calcium transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Salivary gland fluid secretion following neurotransmitter stimulation is Ca2+-dependent. We have studied the control of cellular Ca2+ following secretory stimuli in rat parotid gland acinar cells. After muscarinic-cholinergic receptor activation, cytosolic Ca2+ is elevated 4–5 fold, due to both intracellular Ca2+ pool mobilization and extracellular Ca2+ entry. Fluid movement ensues due to the Ca2+-activated enhancement of membrane permeability to K+ and Cl−. Basal cytosolic Ca2+ levels are tightly controlled at ∼150–200 nM through the action of high affinity and high capacity ATP-dependent Ca2+ transporters in the basolateral and endoplasmic reticulum membranes. Activity of these Ca2+ transporters can be modulated to facilitate rapid responsiveness and a sustained fluid secretory response necessary for alimentary function.
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    Ca2+ ionophores inhibit superoxide generation by chemotactic peptide in rabbit neutrophils and the correlation with intracellular calcium (1988)
    Springer
    Molecular and cellular biochemistry 84 (1988), S. 97-103 
    Details
    ISSN: 1573-4919
    Keywords: neutrophils ; A23187 ; lasalocid ; calcium ; superoxide ; chemotactic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Effects of Ca2+ ionophores, A23187 and lasalocid, on superoxide anion generation by chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine methyl ester, in rabbit peritoneal exudate neutrophils were studied. The ionophores by themselves did not activate superoxide anion generation in these neutrophils. When preincubated with the cells for 2 min, both the ionophores inhibited superoxide generation induced by chemotactic peptide. The inhibition was present even in the absence of extracellular Ca2+ and the inhibition was better then. Lasalocid produces a dose-dependent chlortetracycline fluorescence decrease response in neutrophils loaded with chlortetracycline. This response is independent of extracellular Ca2+ concentration and is related to release of Ca2+ from intracellular storage sites. The dose-range at which lasalocid gives this response is same as the dose-range at which it causes inhibition of superoxide response. It may be concluded that the inhibition of superoxide generation by these ionophores is correlated to intracellular Ca2+ modulation.
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    The contribution of mitochondrial calcium ion exchange to relaxation of tension in cardiac muscle (1989)
    Springer
    Molecular and cellular biochemistry 89 (1989), S. 127-133 
    Details
    ISSN: 1573-4919
    Keywords: mitochondria ; sarcoplasmic reticulum ; calcium ; myocytes ; caffeine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The possible contribution of mitochondrial Ca2+ accumulation and release to contractile phenomena has been investigated. Two intracellular fractions of Ca2+ sequestration can be identified in cardiac myocytes, one ascribed to mitochondria. Two modes of Ca2+ transport exist within the mitochondrial fraction, one dependent upon mitochondrial respiration and the other upon extramitochondrial [Na+]. Experiments with trabeculae show that under appropriate conditions, the rate of relaxation and the amount of tension developed is dependent on these two modes of Ca2+ transport. A model is presented quantifying the contribution of the mitochondria to relaxation.
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    The control of calcium influx by cytoplasmic calcium in mammalian heart muscle (1989)
    Springer
    Molecular and cellular biochemistry 89 (1989), S. 109-113 
    Details
    ISSN: 1573-4919
    Keywords: heart muscle ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The role of Ca2+ in the initiation and maintenance of contraction has been extensively studies. Many of these studies have focused on how Ca2+ influx and efflux affect cytoplasmic Ca2+ (Cai) and, therefore, contraction in cardiac muscle. However, it has recently become apparent that Cai itself may play a major role in the control of Ca2+ influx and efflux from cardiac muscle. Here we review current ideas on the mechanisms underlying Ca2+ homeostasis in cardiac muscle, with specific attention to how Cai may control Ca2+ influx, both under normal and pathological conditions.
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    Redistribution of subcellular calcium in rat liver on administration of vanadate (1989)
    Springer
    Molecular and cellular biochemistry 90 (1989), S. 155-164 
    Details
    ISSN: 1573-4919
    Keywords: polyvanadate ; mitochondria ; calcium ; pyruvate dehydrogenase ; receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary Mitochondria isolated from the livers of rats administered with sodium meta-, ortho-, or polyvanadate, but not vanadyl sulphate, exhibited enhanced Ca2+ — stimulated respiration and uptake of calcium. These effects were shown also by mitochondria isolated from livers perfused with polyvanadate. The concentration of acid-soluble calcium decreased significantly in the mitochondrial fraction on vanadate treatment, while that in the cytosol showed a corresponding increase. Phenoxybenzamine, an antagonist to a-adrenergic receptors, effectively inhibited vanadate-induced Ca2+ mobilization, but surgical sympathectomy was without effect. This is the first demonstration of vanadate mimicking α-adrenergic agonists in vivo.
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    The influence of harmaline on the movements of sodium ions in smooth muscle of the guinea pig ileum (1985)
    Springer
    Molecular and cellular biochemistry 67 (1985), S. 145-150 
    Details
    ISSN: 1573-4919
    Keywords: calcium ; harmaline ; smooth muscle ; sodium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of changing the extracellular concentration of both Na+ and K+ on the longitudinal muscle of the guinea-pig ileum was studied in the presence and absence of harmaline. A decrease in extracellular Na+ concentration was found to produce a dose-dependent contractile response, which may suggest the existence of a Na...Ca exchange mechanism in this muscle. Harmaline (2 × 10−4 M) was found to reversibly inhibit this contraction and was also found to selectively block the tonic component of high-K induced contradictions. In view of the fact that harmaline is a non-competitive inhibitor of Ca-induced contractions (Hider et al., Europ. J. Pharmacol., 71, 87, 1981), the action of harmaline was interpreted as being a specific inhibitor of the Na... exchange mechanism, binding specifically to Na+ coordination sites.
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    Pancreatic islets contain the M2 isoenzyme of pyruvate kinase its phosphorylation has no effect on enzyme activity (1985)
    Springer
    Molecular and cellular biochemistry 68 (1985), S. 115-120 
    Details
    ISSN: 1573-4919
    Keywords: pyruvate kinase isoenzymes ; pancreatic islets ; kinetic and immunological studies ; calcium ; alanine ; phenylalanine ; fructose bisphosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract To determine which of the major isoenzymes of pyruvate kinase pancreatic islet pyruvate kinase most resembled, it was compared to pyruvate kinase from other tissues in kinetic and immunologic studies. The pattern of activation by fructose bisphosphate and the patterns of inhibition by alanine and phenylalanine were most similar to those of the M2 isoenzyme from kidney and were dissimilar to those of the isoenzymes from skeletal muscle (type M1) and liver (type L). The islet pyruvate kinase was inhibited by anti-M1 pyruvate kinase serum (which crossreacts with the M2 isoenzyme), but not by anti-L pyruvate kinase. These results are most consistent with islets possessing predominantly, if not exclusively, the M2 isoenzyme of pyruvate kinase. We previously showed that rat pancreatic islet cytosol contains protein kinases that can catalyze a calcium-activated phosphorylation of an endogenous peptide that has properties, such as subunit molecular weight and isoelectric pH, that are identical to those of the M2 and M, isoenzymes of pyruvate kinase, and that islet cytosol can catalyze phosphorylation of muscle pyruvate kinase. In the present study it was shown that incubating islet cytosol with ATP under conditions known to permit phosphorylation and inhibition of liver pyruvate kinase did not affect the islet pyruvate kinase activity. It is concluded that phosphorylation of the islet pyruvate kinase has no immediate effect on enzyme activity.
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    Dissociation of the metabolic from the contractile response to muscarinic stimulation in the rabbit urinary bladder (1988)
    Springer
    Molecular and cellular biochemistry 81 (1988), S. 137-143 
    Details
    ISSN: 1573-4919
    Keywords: bladder ; muscarinic stimulation ; metabolism ; bethanecol ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The calcium dependence of contraction and NADH flurorescence was investigated in rabbit bladder stimulated with bethanechol or KCl. The absence of calcium in the bathing solution induced a rightward shift in the dose response to bethanechol for both contraction and NADH flurorescence. The contractile response was shifted to a greater degree than the fluorescence response and the maximal response to bethanechol was reduced by 80% for contraction but only 20% for NADH fluorescence. This rightward shift was also induced by the benzothiazepine calcium antagonist diltiazem (200 μM) and again the contractile response was shifted significantly more than the fluorescence response. The combination of zero calcium and 200 μM diltiazem virtually abolished contractions but only inhibited the NADH fluorescence by 65% at maximally effective bethanechol concentrations. Unlike the effect of diltiazem on the response to bethanechol, diltiazem (200 μM) shifted both the contraction and fluorescence curves to the right equally in response to KCl stimulation. These results indicate that a metabolic response to muscarinic stimulation (decreased NADH) can occur in the absence of any observable contractile response. This metabolic response may be due to post receptor signal processing events. For KCl stimulation, the NADH response is probably secondary to and a result of the contractile response.
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    Regulation of exocytosis in electrically permeabilized insulin-secreting cells. Evidence for Ca2+ dependent and independent secretion (1987)
    Springer
    Bioscience reports 7 (1987), S. 443-454 
    Details
    ISSN: 1573-4935
    Keywords: calcium ; exocytosis ; insulin secretion ; permeabilized cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The regulation of insulin secretion from RINm5F cells exposed to high voltage discharge has been investigated. Electron microscopy revealed that the overall structure of the cells was preserved after permeabilization. In this preparation insulin release was stimulated by Ca2+ (EC50=2.4 μM). The stable GTP analogue GTPγS enhanced secretion both at intermediate (nano- to micromolar) and vanishingly low (〈10 pM) Ca2+ concentrations. At optimal Ca2+ (10 μM) the effect of GTPγS was greatly reduced. We investigated whether the secretory response to GTP analogues was mediated by any of three enzyme systems regulated by GTP-binding proteins, i.e. generation of cyclic AMP by adenylate cyclase, of diacylglycerol by phospholipase C and of arachidonic acid by phospholipase A2. The involvement of these messenger systems could be excluded as (i) cyclic AMP only had minor, Ca2+ dependent effects, (ii) phospholipase C was not activated in the absence of Ca2+ and insulin secretion due to the phorbol ester TPA displayed a different Ca2+ dependency, (iii) arachidonic acid did not elicit Ca2+ independent insulin secretion. These results, taken together with the finding that insulin secretion due to Ca2+ or TPA is attenuated by the inhibitory guanine nucleotide GDPβS, suggest the existence of a regulatory site in exocytosis which is sensitive to guanine nucleotides.
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    A novel role of Ca2+ and Zn2+: Protection of cells against membrane damage (1988)
    Springer
    Bioscience reports 8 (1988), S. 579-583 
    Details
    ISSN: 1573-4935
    Keywords: calcium ; zinc ; membrane protection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Certain cytotoxic agents damage cells by the induction of pores across their plasma membrane. Ca2+ and Zn2+ protect against such damage by promoting pore closure. Zn2+ may play a beneficial role in this regard in certain disease states.
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    URL: http://dx.doi.org/10.1007/BF01117337
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    ATP inhibits onset of exocytosis in permeabilised mast cells (1989)
    Springer
    Bioscience reports 9 (1989), S. 99-109 
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    ISSN: 1573-4935
    Keywords: mast cells ; exocytosis ; G-protein ; GE ; calcium ; ATP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract ATP is not required for exocytosis from permeabilised mast cells, and therefore there is no direct role for protein phosphorylation in the late stages of the activation pathway. We have measured the timecourse of exocytosis from permeabilised cells triggered to release hexosaminidase following addition of Ca2+ to cells equilibrated for 2 min with GTP-γ-S. If ATP is included at the time of permeabilisation, then exocytosis commences after a delay, the duration of which depends on the square root of the product [Ca2+][GTP-γ-S], and which may extend to beyond 3 min. When ATP is excluded then the maximal rate of exocytosis is established within 3 secs of completing the effector combination. These results suggest that the achievement of a new steady-state, induced by Ca2+ and GTP-γ-S, and required for exocytosis is inhibited by ATP. From this we conclude that dephosphorylation of an unknown regulator protein may comprise a step in the exocytotic pathway.
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    URL: http://dx.doi.org/10.1007/BF01117516
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    Defective regulation of apical membrane chloride transport and exocytosis in cystic fibrosis (1988)
    Springer
    Bioscience reports 8 (1988), S. 27-33 
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    ISSN: 1573-4935
    Keywords: cystic fibrosis ; chloride transport ; exocytosis ; calcium ; calmodulin ; B-adrenergic ; cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A biochemical link is proposed between recent observations on defective regulation of Cl− transport in CF respiratory epithelial cells and studies showing altered biological activity of calmodulin in exocrine glands from CF patients. A consensus is emerging that defective β-adrenergic secretory responsiveness in CF cells is caused by a defect in a regulator protein at a site distal to cyclic AMP formation. Our results indicate that this protein might be a specific calmodulin acceptor protein which modifies the activity of calmodulin in epithelial cells. Alteration in Ca2+/calmodulin dependent regulation of Cl− transport and protein secretion could explain (i) alterations in Ca2+ homeostasis seen in CF, (ii) defective β-adrenergic responses of CF cells, and (iii) the observed inability of cyclic AMP (acting via its specific protein kinase, A-kinase) to open apical membrane Cl− channels in CF epithelial cells. Most of the physiological abnormalities of CF including elevated sweat electrolytes and hyperviscous mucus can be explained on this basis.
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    Exocytosis reconstituted from the sea urchin egg is unaffected by calcium pretreatment of granules and plasma membrane (1988)
    Springer
    Bioscience reports 8 (1988), S. 335-343 
    Details
    ISSN: 1573-4935
    Keywords: calcium ; exocytosis ; sea urchin egg ; phosphoinositide ; diacylglycerol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Micromolar calcium ion concentrations stimulate exocytosis in a reconstituted system made by recombining in the plasma membrane and cortical secretory granules of the sea urchin egg. The isolated cortical granules are unaffected by calcium concentrations up to 1 mM, nor do granule aggregates undergo any mutual fusion at this concentration. Both isolated plasma membrane and cortical granules can be pretreated with 1 mM Ca before reconstitution without affecting the subsequent exocytosis of the reconstituted system in response to micromolar calcium concentrations. On reconstitution, aggregated cortical granules will fuse with one another in response to micromolar calcium provided that one of their number is in contact with the plasma membrane. If exocytosis involves the generation of lipid fusogens, then these results suggest that the calcium-stimulated production of a fusogen can occur only when contiguity exists between cortical granules and plasma membrane. They also suggest that a substance involved in exocytosis can diffuse and cause piggy-back fusion of secretory granules that are in contact with the plasma membrane. Our results are also consistent with a scheme in which calcium ions cause a reversible, allosteric activation of an exocytotic protein.
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    Calcium and diacylglycerol control of secretion (1987)
    Springer
    Bioscience reports 7 (1987), S. 355-367 
    Details
    ISSN: 1573-4935
    Keywords: calcium ; diacylglycerol ; exocytosis ; secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Measurements of intracellular Ca2+ in adrenal medullary cells suggest that a transient rise in Ca2+ leads to a transient secretory response, the rise in Ca2+ being brought about by an influx through voltage-sensitive Ca channels which subsequently inactivate. The level of Ca2+ observed is much smaller than the Ca2+ needed to trigger secretion when introduced directly into the cell. The discrepancy is removed by the presence of diacylglycerot, which increases the sensitivity of the secretory process to Ca2+. The site of action of Ca2+ and diacylglycerol is probably protein kinase C, and tile different secretory responses to increases of Ca2+ and diacylglycerol can be modelled in terms of a preferential order of binding of these two substrates to the enzyme. ATP is needed for secretion: one role is possibly to confer stability to the secretory apparatus; another may involve phosphorylation of some key protein. The kinetics of secretion suggest that if Ca2+ regulates phosphorylation or dephosphorylation, then it is therate of change of phosphorylation that controls secretion rather than theextent of phosphorylation or dephosphorylation. Guanine nucleotide-binding proteins may play a role not only at the level of signal transduction coupling, but also at or near the site of exocytosis, and the mechanism by which some Botulinum toxins inhibit secretion may be associated with these proteins.
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    How calcium may cause exocytosis in sea urchin eggs (1987)
    Springer
    Bioscience reports 7 (1987), S. 383-397 
    Details
    ISSN: 1573-4935
    Keywords: calcium ; eggs ; exocytosis ; sea urchin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract The process of secretory granule-plasma membrane fusion can be studied in sea urchin eggs. Micromolar calcium concentrations are all that is required to bring about exocytosisin vitro. I discuss recent experiments with sea urchin eggs that concentrate on the biophysical aspects of granule-membrane fusion. The backbone of biological membranes is the lipid bilayer. Sea urchin egg membrane lipids have negatively charged head groups that give rise to an electrical potential at the bilayer-water interface. We have found that this surface potential can affect the calcium required for exocytosis. Effects on the surface potential may also explain why drugs like trifluoperazine and tetracaine inhibit exocytosis: they absorb to the bilayer and reduce the surface potential. The membrane lipids may also be crucial to the formation of the exocytotic pore through which the secretory granule contents are released. We have measured calcium-induced production of the lipid, diacylglycerol. This lipid can induce a phase transition that will promote fusion of apposed lipid bilayers. The process of exocytosis involves the secretory granule core as well as the lipids of the membrane. The osmotic properties of the granule contents lead to swelling of the granule during exocytosis. Swelling promotes the dispersal of the contents as they are extruded through the exocytotic pore. The movements of water and ions during exocytosis may also stabilize the transient fusion intermediate and consolidate the exocytotic pore as fusion occurs.
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    A comparison of bradykinin, angiotensin II and muscarinic stimulation of cultured bovine adrenal chromaffin cells (1989)
    Springer
    Bioscience reports 9 (1989), S. 243-252 
    Details
    ISSN: 1573-4935
    Keywords: secretion ; exocytosis ; chromaffin cell ; calcium ; bradykinin ; angiotensin II, muscarinic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Bradykinin, angiotensin II and a mascarnic agonist, acetyl-B-methacholine (methacholine) were all found to elict catecholamine release from cultured bovine adrenal chromaffin cells. Bradykinin was the most potent of these secretagogues and methacholine the weakest, with angiotenin II intermediate in efficacy. All three secretagogues were much less effective than nicotinic stimulation. The three secretagogues all produced a rise in cytoplasmic free calcium concentration ([Ca2+]i), measured with the fluorescent indicator fura2, which was partially independent of external calcium. In the case of bradykinin the full rise in ([Ca2+]i) may involve a component of calcium entry in addition to release of calcium from an internal store. Secretion was also found to be partially independent of external calcium. The different efficacies of the three secretagogues in elicting secretion were correlated with the rise in ([Ca2+]i) produced. The differeing efficacies of the three secretagogues may be due to the extent of release of calcium from an intracellular store which itself is less effective in eliciting secretion than a rise in [Ca2+]i following calcium entry due to nicotine. Bradykinin also stimulates calcium entry, and this may increase the efficacy of the initial rise in [Ca2+]i. Treatment with pertussis toxin resulted in an enhancement of secretion in response to all of the secretagogues.
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    The molecular and biochemical basis of cystic fibrosis (1987)
    Springer
    Bioscience reports 7 (1987), S. 167-185 
    Details
    ISSN: 1573-4935
    Keywords: cystic fibrosis ; exocrine ; autonomic ; cyclic AMP ; calcium ; chloride ; epithelial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
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    URL: http://dx.doi.org/10.1007/BF01124787
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    A nonselective cation channel activated by membrane deformation in oocytes of the ascidianBoltenia villosa (1989)
    Springer
    The journal of membrane biology 107 (1989), S. 179-188 
    Details
    ISSN: 1432-1424
    Keywords: stretch-activated channel ; calcium ; oocyte ; development ; patch clamp ; tunicate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Cell-attached patch clamp recordings from unfertilized oocytes of the ascidianBoltenia villosa reveal an ion channel which is activated by mechanical deformation of the membrane. These channels are seen when suction is applied to the patch pipette, but not in the absence of suction or during voltage steps. The estimated density of these stretch-activated channels is about 1.5/μm2, a figure equal to or greater than the density of known voltage-dependent channels in the oocyte. Ion substitution experiments done with combined whole-cell and attached patch recording, so absolute potentials are known, indicate that the channel passes Na+, Ca2+ and K+, but not Cl−. The channel has at least two open and two closed states, with the rate constant that leaves the longer-lived closed state being the primary site of stretch sensitivity. External Ca2+ concentration affects channel kinetics: at low calcium levels, long openings predominate, whereas at high calcium virtually all openings are to the short-lived open state. In multiple channel patches, the response to a step change in suction is highly phasic, with channel open probability decreasing over several hundred milliseconds to a nonzero steady-state level after an initial rapid increase. This channel may play a role in the physiological response of cells of the early embryo to the membrane strains associated with morphogenetic events.
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    URL: http://dx.doi.org/10.1007/BF01871723
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    Ca2+-activated K+ channels in the apical membrane ofNecturus choroid plexus (1988)
    Springer
    The journal of membrane biology 105 (1988), S. 207-219 
    Details
    ISSN: 1432-1424
    Keywords: choroid plexus ; brush border membrane ; Ca2+-activated K+ channels ; calcium ; barium ; TEA ; intracellular pH ; cerebrospinal fluid secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The properties of Ca2+-activated K+ channels in the apical membrane of theNecturus choroid plexus were studied using single-channel recording techniques in the cell-attached and excised-patch configurations. Channels with large unitary conductances clustered around 150 and 220 pS were most commonly observed. These channels exhibited a high selectivity for K+ over Na+ and K+ over Cs+. They were blocked by high cytoplasmic Na+ concentrations (110mm). Channel activity increased with depolarizing membrane potentials, and with increasing cytoplasmic Ca2+ concentrations. Increasing Ca2+ from 5 to 500nm, increased open probability by an order of magnitude, without changing single-channel conductance. Open probability increased up to 10-fold with a 20-mV depolarization when Ca2+ was 500nm. Lowering intracellular pH one unit, decreased open probability by more than two orders of magnitude, but pH did not affect single-channel conductance. Cytoplasmic Ba2+ reduced both channel-open probability and conductance. The sites for the action of Ba2+ are located at a distance more than halfway through the applied electric field from the inside of the membrane. Values of 0.013 and 117mm were calculated as the apparent Ba2+ dissociation constants (K d (0 mV) for the effects on probability and conductance, respectively. TEA+ (tetraethylammonium) reduced single-channel current. Applied to the cytoplasmic side, it acted on a site 20% of the distance through the membrane, with aK d (0 mV)=5.6mm. A second site, with a higher affinity,K d (0 mV)=0.23mm, may account for the near total block of chanel conductance by 2mm TEA+ applied to the outside of the membrane. It is concluded that the channels inNecturus choroid plexus exhibit many of the properties of “maxi” Ca2+-activated K+ channels found in other tissues.
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    Ca2+-activated K+ currents inNecturus choroid plexus (1988)
    Springer
    The journal of membrane biology 105 (1988), S. 221-231 
    Details
    ISSN: 1432-1424
    Keywords: choroid plexus ; calcium-activated potassium currents ; cerebrospinal fluid secretion ; calcium ; delayed currents ; patch clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The tight-seal whole-cell recording method has been used to studyNecturus choroid plexus epithelium. A cell potential of −59±2 mV and a whole cell resistance of 56±6 MΩ were measured using this technique. Application of depolarizing step potentials activated voltage-dependent outward currents that developed with time. For example, when the cell was bathed in 110mm NaCl Ringer solution and the interior of the cell contained a solution of 110mm KCl and 5nm Ca2+, stepping the membrane potential from a holding value of −50 to −10 mV evoked outward currents which, after a delay of greater than 50 msec, increased to a steady state in 500 msec. The voltage dependence of the delayed currents suggests that they may be currents through Ca2+-activated K_ channels. Based on the voltage dependence of the activation of Ca2+-activated K+ channels, we have devised a general method to isolate the delayed currents. The delayed currents were highly selective for K+ as their reversal potential at different K+ concentration gradients followed the Nernst potential for K+. These currents were reduced by the addition of TEA+ to the bath solution and were eliminated when Cs+ or Na+ replaced intracellular K+. Increasing the membrane potential to more positive values decreased both the delay and the half-times (t 1/2) to the steady value. Increasing the pipette Ca2+ also decreased the delay and decreasedt 1/2. For instance, when pipette Ca2+ was increased from 5 to 500nm, the delay andt 1/2 decreased from values greater than 50 and 150 msec to values less than 10 and 50 msec. We conclude that the delayed currents are K+ currents through Ca2+-activated K+ channels. At the resting membrane potential of −60 mV, Ca2+-activated K+ channels contribute between 13 to 25% of the total conductance of the cell. The contribution of these channels to cell conductance nearly doubles with membrane depolarization of 20–30 mV. Such depolarizations have been observed when cerebrospinal fluid (CSF) secretion is stimulated by cAMP and with intracellular Ca2+. Thus the Ca2+-activated K+ channels may play a specific role in maintaining intracellular K+ concentrations during CSF secretion.
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    Tight junction formation in cultured epithelial cells (MDCK) (1985)
    Springer
    The journal of membrane biology 86 (1985), S. 113-125 
    Details
    ISSN: 1432-1424
    Keywords: epithelial monolayers ; MDCK cells ; tight junctions ; calcium ; biosynthesis of junctions ; junctional assembly ; apical/basolateral polarization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Synthesis and assembly of tight junctions are studied in monolayers of MDCK cells plated at a density sufficient for confluence, allowed to attach for 1 hr, and transferred to fresh media without cells containing or not Ca2+, 20 hr later, while monolayers with Ca2+ have fully developed junctions that confer an electrical resistance across of 346±51 Ω cm2, those without Ca2+ have a negligible resistance. If at this time Ca2+ is added, junctions assemble and seal with a fast kinetics, that can be followed through the development of electrical resistance, penetration of ruthenium red, and electron microscopy. Drugs that impair synthesis, maturation and transport of proteins (cycloheximide, tunicamycin, monensin) indicate that protein components are synthesized early upon plating, do not seem to require N-glycosylation, and are stored in the Golgi compartment. Upon addition of Ca2+ they are transferred to the membrane with the participation of microfilaments but not of microtubules. These components seem to insert directly in the position they occupy in the strands, and the cell circles its perimeter with one strand as early as 15 min, even if in some segments it only consists of a row of particles. New strands develop in association with previous ones, and the pattern completes in 4 to 6 hr. Ca2+ is required for the maintenance of the assembly and also for the sealing with neighboring cells. These processes cannot occur below 25°C. Serum is not required. Polarized distribution of intramembrane particles (IMP) in apical and basolateral regions follows the same time course as junction formation, in spite of the fence constituted by those strands that are already assembled. This suggests that IMP do not redistribute by lateral displacements in the plane of the membrane, but by removal and insertion in the apical and basolateral domains.
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    Electric pulse-induced fusion of mouse lymphoma cells: Roles of divalent cations and membrane lipid domains (1985)
    Springer
    The journal of membrane biology 85 (1985), S. 269-280 
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    ISSN: 1432-1424
    Keywords: cell fusion ; electrofusion ; dielectrophoresis ; calcium ; magnesium ; membrane lipid ; lymphoma cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Mouse leukemic lymphoblasts (L5178Y) brought into close contact by dielectrophoresis underwent cell fusion following the application of electrical pulses in the presence of electrolytes. The electrically fused cells became spherical after switching off the dielectrophoretic field. Fusion between a cell vitally stained with Janus Green and that with Neutral Red resulted in the homokaryon with a mixed color. Intracellular potentials simultaneously recorded from the two cells located on both sides of the homokaryon were identical. The fusion efficiency was remarkably dependent upon temperature, displaying a discontinuity at about 11°C in the Arrhenius plot. The extracellular application of phospholipase-A2 or-C suppressed the fusion yield. Thus, it appears that the phospholipid domains play a crucial role in the electric pulse-induced cell fusion. Treatment of the cells with proteolytic enzymes markedly enhanced the fusion yield, presumably due to removing the glycocalix and/or giving rise to fusion-potent, protein-free lipid domains. The presence of millimolar concentrations of divalent cations (irrespective of Mg2+ or Ca2+) as well as of micromolar concentrations of Ca2+ (but not Mg2+) was prerequisite to the resealing of membranes suffered from electrical breakdown upon exposure to electric pulses. In addition, extracellular Ca2+ (but not Mg2+) ions at more than micromolar concentrations were indispensable for the cell fusion.
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    Single Cl− channels in molluscan neurones: Multiplicity of the conductance states (1985)
    Springer
    The journal of membrane biology 86 (1985), S. 9-15 
    Details
    ISSN: 1432-1424
    Keywords: molluscan neurone ; patch voltage-clamp technique ; single Cl channel ; calcium ; potassium ; multiplicity of the condutance states
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Properties of the single Cl− channels were studied in excised patches of surface membrane from molluscan neurones using single-channel recording technique. These channels are controlled by Ca2+ and K+ acting on cytoplasmic and outer membrane surfaces, respectively, and by the membrane potential. The channels display about 16 intermediate conductance sublevels, each of them being multiples of ∼12.5 pS. The upper level of the channel conductance is about 200 pS. The channel behavior is consistent with an aggregation of channel-forming subunits into a cluster.
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    The role of phosphoinositiees in signal transduction (1986)
    Springer
    The journal of membrane biology 89 (1986), S. 193-210 
    Details
    ISSN: 1432-1424
    Keywords: phosphoinositides ; phosphatidylinositol ; inositol-1,4,5-trisphosphate ; diacylglycerol ; arachidonic acid ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01870664
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    The chromaffin granule proton pump and calcium-dependent exocytosis in bovine adrenal medullary cells (1985)
    Springer
    The journal of membrane biology 83 (1985), S. 147-156 
    Details
    ISSN: 1432-1424
    Keywords: Exocytosis ; proton pump ; calcium ; secretion ; adrenal medulla
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Calcium-dependent exocytosis in ‘leaky’ bovine adrenal medullary cells has a requirement for Mg-ATP. One possibility is that exocytosis depends in some way on the operation of the ATP-dependent proton pump that serves to maintain the core of the secretory vesicles both acid and at a positive potential with respect to the cytosol. This possibility has been tested in ‘leaky’ cells by monitoring exocytosis under conditions where the secretory vesicle pH and potential gradients are measuredin situ. The results show rather clearly that exocytosis can persist, with unchanged Ca-activation kinetics, in the virtual absence both of a difference in pH between the cytosol and secretory vesicle core and also of a difference in potential across the vesicle membrane. The results do not, however, exclude a small modulating effect of vesicle pH or potential on exocytosis and shed no light on whether or not the plasma membrane potential, which is maintained close to zero in these experiments, influences exocytosis.
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    URL: http://dx.doi.org/10.1007/BF01868746
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    Effects of membrane potential on sodium-dependent calcium uptake by sarcolemma-enriched preparations from canine ventricle (1985)
    Springer
    The journal of membrane biology 84 (1985), S. 207-219 
    Details
    ISSN: 1432-1424
    Keywords: sodium/calcium exchange ; excitation-contraction coupling ; sarcolemma ; membrane potential ; sodium ; calcium ; heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The effect of membrane potential on sodium-dependent calcium uptake by vesicles in an isolated cardiac sarcolemma preparation was examined. Initial time course studies showed that the reaction deviated from initial velocity conditions within minutes. This appeared to be due, in part, to loss of the sodium gradient. Assays carried out to 10 sec revealed a linear component of uptake (2 to 10 sec) and a faster component (complete by 2 sec). The latter was eliminated by loading the preparation with ethyleneglycol-bis-(β-aminoethyl ether)N,N′-tetraacetic acid (EGTA). This maneuver did not affect the slow component, and subsequent studies used preparations containing EGTA. Potassium Nernst potentials (E K), established by potassium gradients in the presence of valinomycin, were varied from −100 to +30 mV by changing [K+] o from 1.18 to 153.7mM ([K+] i =50mM). The initial velocity of sodium-dependent calcium uptake was stimulated twofold by changingE K from −100 to 0 mV and another twofold by raisingE K from 0 to +30 mV. For the total range ofE K and [K+] o , 32 to 36% of the increase appeared to reflect stimulation by extravesicular potassium. The remainder appeared to be due to membrane potential. The profile of sodium-dependent calcium uptake versusE K suggested that calcium influx through electrogenic sodium/calcium exchange may be much more affected by the positive region of the cardiac action potential than by the negative region.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01871384
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    Ca2+ buffer sites in intact bovine rod outer segments: Introduction to a novel optical probe to measure ionic permeabilities in suspensions of small particles (1985)
    Springer
    The journal of membrane biology 88 (1985), S. 249-262 
    Details
    ISSN: 1432-1424
    Keywords: calcium ; rod photoreceptors ; surface potentials
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The nature of the Ca2+ buffer sites in intact rod outer segments isolated from bovine retinas (ROS) was investigated. The predominant Ca2+ buffer in intact ROS was found to be negatively charged groups confined to the surface of the disk membranes. Accordingly, Ca2+ buffering in ROS was strongly influenced by the electrostatic surface potential. The concentration of Ca2+ buffer sites was about 30mm, 80% of which were located at the membrane surface in the intradiskal space. A comparison with observations in model systems suggests that phosphatidylserine is the major Ca2+ buffer site in ROS. Protons and alkali cations could replace Ca2+ as mobile counterions for the fixed negatively charged groups. At physiological ionic strength, the total number of these diffusible, but osmotically inactive, counterions was as large as the number of osmotically active cations in ROS. The surface potential is dependent on the concentration of cations in ROS and can be measured with the optical dye neutral red. Addition of cations to the external solution led to the release of the internally bound dye as the cations crossed the outer membrane. The chemical and spectral properties of the dye enable its use as a real-time indicator of cation transport across the outer envelope of small particles in suspension. In this study, the dye method is illustrated by the use of well-defined ionophores in intact ROS and in liposomes. In the companion paper this method is used to describe the cation permeabilities native to ROS.
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    URL: http://dx.doi.org/10.1007/BF01871089
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    Electrophysiological evidence suggests a defective Ca2+ control mechanism in a newParamecium mutant (1987)
    Springer
    The journal of membrane biology 98 (1987), S. 275-283 
    Details
    ISSN: 1432-1424
    Keywords: Paramecium ; calcium ; cilia ; mutants ; Ca2+ pump ; Ca2+ buffering ; ion channels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary A new mutant ofParamecium tetraurelia, k-shyA, was characterized behaviorally and electrophysiologically. The mutant cell exhibited prolonged backward swimming episodes in response to depolarizing conditions. Electrophysiological comparison of k-shyA with wild type cells under voltage clamp revealed that the properties of three Ca2+-regulated currents were altered in the mutant. (i) The voltage-dependent Ca2+ current recovered from Ca2+-dependent inactivation two- to 10-fold more slowly than wild type. Ca2+ current amplitudes were also reduced in the mutant, but could be restored by EGTA injection. (ii) The decay of the Ca2+-dependent K+ tail current was slower in the mutant. (iii) The decay of the Ca2+-dependent Na+ tail current was also slower in the mutant. All other membrane properties studied, including the resting membrane potential and resistance and the voltage-sensitive K+ currents, were normal in k-shyA. Considered together, these observations are consistent with a defect in the ability of k-shyA to reduce the free intracellular Ca2+ concentration following stimulation. The possible targets of the genetic lesion and alternative explanations are discussed. The k-shy mutants may provide a useful tool for molecular and physiological analyses of the regulation of Ca2+ metabolism inParamecium.
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    URL: http://dx.doi.org/10.1007/BF01871189
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  • 199
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    Na+/K+/Cl− cotransport in cultured vascular smooth muscle cells: Stimulation by angiotensin II and calcium ionophores, inhibition by cyclic AMP and calmodulin antagonists (1987)
    Springer
    The journal of membrane biology 99 (1987), S. 51-63 
    Details
    ISSN: 1432-1424
    Keywords: endothelial cells ; Na+/K+/Cl− cotransport ; cyclic AMP ; phenothiazines ; calcium ; angiotensin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The specific activity of the Na+/K+/Cl− cotransporter was assayed by measuring the initial rates of furosemide-inhibitable86Rb+ influx and efflux. The presence of all three ions in the external medium was essential for cotransport activity. In cultured smooth muscle cells furosemide and bumetanide inhibited influx by 50% at 5 and 0.2 μm, respectively. The dependence of furosemide-inhibitable86Rb+ influx on external Na+ and K+ was hyperbolic with apparentK m values of 46 and 4mm, respectively. The dependence on Cl− was sigmoidal. Assuming a stoichiometry of 1∶1∶2 for Na+/K+/Cl−, aK m of 78mm was obtained for Cl−. In quiescent smooth muscle cells cotransport activity was approximately equal to Na+ pump activity with each pathway accounting for 30% of total86Rb+ influx. Growing muscle cells had approximately 3 times higher cotransport activity than quiescent ones. Na+ pump activity was not significantly different in the gorwing and quiescent cultures. Angiotensin II (ANG) stimulated cotransport activity as did two calcium-transporting ionophores, A23187 and ionomycin. The removal of external Ca2+ prevented A23187, but not ANG, from stimulating the cotransporter. Calmodulin antagonists selectively inhibited86Rb+ influx via the cotransporter. Beta-adrenoreceptor stimulation with isoproterenol, like other treatments which increase cAMP, inhibited cotransport activity. Cultured porcine endothelial cells had 3 times higher cotransport activity than growing muscle cells. Calmodulin antagonists inhibited cotransport activity, but agents which increase cAMP or calcium had no effect on cotransport activity in the endothelial cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01870621
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    Role of calcium and calmodulin in the regulation of the rabbit ileal brush-border membrane Na+/H+ antiporter (1989)
    Springer
    The journal of membrane biology 108 (1989), S. 207-215 
    Details
    ISSN: 1432-1424
    Keywords: calcium ; calmodulin ; absorption ; ileum ; brush-border vesicle ; phosphorylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary In rabbit ileum, Ca2+/calmodulin (CaM) appears to be involved in physiologically inhibiting the linked NaCl absorptive process, since inhibitors of Ca2+/CaM stimulate linked Na+ and Cl− absorption. The role of Ca2+/CaM-dependent phosphorylation in regulation of the brush-border Na+/H+ antiporter, which is believed to be part of the neutral linked NaCl absorptive process, was studied using purified brush-border membrane vesicles, which contain both the Na+/H+ antiporter and Ca2+/CaM-dependent protein kinase(s) and its phosphoprotein substrates. Rabbit ileal villus cell brush-border membrane vesicles were prepared by Mg precipitation and depleted of ATP. Using a freezethaw technique, the ATP-depleted vesicles were loaded with Ca2+, CaM, ATP and an ATP-regenerating system consisting of creatine kinase and creatine phosphate. The combination of Ca2+/CaM and ATP inhibited Na+/H+ exchange by 45±13%. This effect was specific since Ca2+/CaM and ATP did not alter diffusive Na+ uptake, Na+-dependent glucose entry, or Na+ or glucose equilibrium volumes. The inhibition of the Na+/H+ exchanger by Ca2+/CaM/ATP was due to an effect on theV max and not on theK m for Na+. In the presence of CaM and ATP, Ca2+ caused a concentration-dependent inhibition of Na+ uptake, with an effect 50% of maximum occurring at 120nm. This Ca2+ concentration dependence was similar to the Ca2+ concentration dependence of Ca2+/CaM-dependent phosphorylation of specific proteins in the vesicles. The Ca2+/CaM/ATP-inhibition of Na+/H+ exchange was reversed by W13, a Ca2+/CaM antagonist, but not by a hydrophobic control, W12, or by H-7, a protein kinase C antagonist. we conclude that Ca2+, acting through CaM, regulates ileal brush-border Na+/H+ exchange, and that this may be involved in the regulation of neutral linked NaCl absorption.
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    URL: http://dx.doi.org/10.1007/BF01871735
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