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  • Articles  (63)
  • hypertension  (61)
  • 42.55
  • 42.80
  • Coleoptera
  • Springer  (63)
  • Annual Reviews
  • Blackwell Publishing Ltd
  • Wiley
  • 2005-2009
  • 1990-1994  (38)
  • 1980-1984  (25)
  • 1991  (10)
  • 1990  (28)
  • 1981  (25)
  • Medicine  (63)
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  • Articles  (63)
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  • Springer  (63)
  • Annual Reviews
  • Blackwell Publishing Ltd
  • Wiley
Years
  • 2005-2009
  • 1990-1994  (38)
  • 1980-1984  (25)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 46 (1990), S. 700-704 
    ISSN: 1420-9071
    Keywords: Coleoptera ; Tenebrionidae ; Tribolium confusum ; defesive secretion ; biosynthesis of 1-alkenes ; oxidative decarboxylation ; anti-elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The terminally unsaturated hydrocarbons of the defensive secretion ofTribolium confusum are biosynthesized from fatty acids by oxidative decarboxylation. The process involves an enantiospecific cleavage of the C−H bond of thepro-(S) C(3)−H atom and simultaneous decarboxylation of the acid into an 1-alkene and carbon dioxide via ananti-periplanar transition state geometry (anti-elimination). The stereochemistry of this biotranformation is identical in all respects with the same reaction in higher plants. The mechanism seems to be of general importance for the biosynthesis of many vinylic substructures of natural products from oxygen-containing precursors.
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  • 2
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    Springer
    Cellular and molecular life sciences 46 (1990), S. 1209-1211 
    ISSN: 1420-9071
    Keywords: Pheromone ; E-myrcenol ; ipsdienol ; Ips duplicatus ; Coleoptera ; Scolytidae ; Picea abies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Males of the Eurasian bark beetleIps duplicatus, when feeding in host Norway spruce (Picea abies (L.) Karst.), produced and released ipsdienol andE-myrcenol, which we show to be aggregation pheromone components. Bioassays using walking beetles indicated thatE-myrcenol in synergistic combination with ipsdienol is essential for attraction. Synergism ofE-myrcenol and ipsdienol released at natural rates in the forest was also demonstrated with a new technique using mechanical slow-rotation of sticky traps.
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  • 3
    ISSN: 1432-1041
    Keywords: Atenolol ; hypertension ; ß-adrenoceptor blockade ; blood pressure ; heart rate ; ambulatory ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 4
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    European journal of clinical pharmacology 39 (1990), S. 435-439 
    ISSN: 1432-1041
    Keywords: co-dergocrine mesylate ; hypertension ; aldosterone ; catecholamines ; nifedipine ; renin side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Co-dergocrine mesylate (Cod), which inhibits norepinephrine secretion by stimulating presynaptic dopamine receptors, and has no known metabolic side effect, has an additive antihypertensive effect to that of Nifedipine (Nif). Plasma norepinephrine, epinephrine, renin activity and aldosterone have been measured after acute administration of Nif and Cod alone and in combination to 18 patients with a diastolic blood pressure 〉 105 mm Hg in a cross-over, randomized, double-blind study. Every patient received 4 mg Cod then 20 mg Nif, placebo then 20 mg Nif and 4 mg Cod then placebo. The second treatment was always given 1 h after the first medication. Blood pressure was measured before and every 15 min during the study period. Blood for measurement of catecholamines, aldosterone and renin activity was collected before medication, 1 h after the first dose and 90 min after the second treatment. Blood pressure was significantly lower (P 〈 0.05) where Cod preceded Nif. Cod caused a significant decrease in plasma norepinephrine from 293 to 202 pg · ml−1 and in epinephrine from 67 to 55 pg · ml−1. The Nif-induced increase in norepinephrine from a pre-treatment value of 293 pg · ml−1 with preceding Cod to 331 pg · ml−1 was much less than the increase with placebo as premedication, from 284 to 440 pg · ml−1. Nif caused an increase in renin activity but no increase in aldosterone. Nif-related side effects, such as flushing and headache, occurred in 6 patients of whom 5 had no received Cod as premedication. Due to the stabilizing action of Cod on catecholamines and on the side effects of Nif, Cod may be preferable to other antihypertensives in augmenting the antihypertensive action of Nif.
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  • 5
    ISSN: 1432-1041
    Keywords: Insulin secretion ; Nifedipine ; non insulin-dependent-diabetes mellitus- ; hyperglycaemia ; plasma insulin ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of 7-days of nifedipine treatment on insulin secretion has been analyzed in hypertensive patients with non-insulin-dependent mellitus (NIDDM). Pancreatic β-cell function was assessed as insulin release following stimulation with arginine after potentiation by hyperglycaemia. Two groups of 5 patients with NIDDM (fasting blood glucose 139.2 mg·dl−1), on the same controlled diet, were compared; one was treated with nifedipine 30 mg per d and the other was the control. The mean blood pressure in the nifedipine group decreased (110 vs 102 mm Hg). Fasting blood glucose and basal plasma insulin were not affected by nifedipine. The acute insulin response (AIR) to 5 g arginine after potentiation by hyperglycaemia (clamped at 240 and 350 mg/dl for 30 min) was significantly (P〈0.05) decreased, as well as the potentiation slope (line relating AIR and plasma glucose level) in those patients, and were unchanged in the control group. Thus, nifedipine may impair insulin secretion at high glucose levels in patients with NiDDM.
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  • 6
    ISSN: 1432-1041
    Keywords: arrhythmia ; hypertension ; LVH ; holter monitoring ; BP monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the relationship among supraventricular and ventricular arrhythmias with blood pressure and heart rate (HR) values, we studied 2 groups of 20 hypertensive men with (group I) and without (group II) left ventricular hypertrophy. Ambulatory electrocardiographic tracings were recorded continuously, together with ambulatory arterial pressure. Systolic (SBP) and diastolic (DBP) blood pressure values measured over 24 h showed no difference between the two groups, but we found greater variability in SBP in group I. The incidence of ventricular and supraventricular arrhythmias was significantly higher in patients of group I; moreover, we found a strong correlation between the incidence of ventricular extrasystoles (VPCs) and SBP, DBP, and HR values in group I, whereas in group 11 the incidence of supraventricular extrasystoles (APCs) was higher during peaks of SBP and HR values. The relationship between APCs and SBP observed in group II may be attributable to the pressure stimulus on a normal atrium, and the significant correlation between VPCs and SBP, DBP, and HR values may be due to episodes of subendocardial ischemia or to the influence of adrenergic stimulation on previously compromised myocardial tissue.
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  • 7
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    Springer
    European journal of clinical pharmacology 38 (1990), S. 209-211 
    ISSN: 1432-1041
    Keywords: Isradipine ; hypertension ; pharmacokinetics ; pharmacodynamics ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In conjunction with a multicentre clinical trial of the calcium antagonist isradipine in hypertension, pharmacokinetic and pharmacodynamic studies were conducted in 9 subjects. An initial dose of 5 mg (capsule formulation) of isradipine was given orally. The mean Cmax, tmax and AUC(0–8) were 6.0 ng · ml−1, 1.5 h and 15.1 h · ng · ml−1 respectively. Seven subjects repeated the study at steady state after 10 week's dose titration with isradipine. Cmax, tmax and AUC(0–8) were 3.7 ng · ml−1, 1.2 h and 12.2 h · ng · ml−1 respectively indicating that the drug does not accumulate over time. Control of blood pressure paralleled plasma isradipine concentrations which suggested that the drug should be given at least twice daily. Pharmacokinetic studies performed in conjunction with clinical trials can provide valuable information about the patterns of drug response.
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  • 8
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    European journal of clinical pharmacology 40 (1991), S. 131-134 
    ISSN: 1432-1041
    Keywords: trimazosin ; hypertension ; alpha1-adrenoceptor blocker ; essential ; exercise ; extracellular fluid volume ; haemodynamics ; plasma volume ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The long-term haemodynamic effect of sustained-release trimazosin (mean daily dose 418 mg) at rest and during exercise has been examined in 14 male patients (age 30–61 y) with previously untreated mild or moderate essential hypertension. Cardiac output (dye dilution), heart rate and intra-arterial blood pressure were measured supine and sitting at rest, and during bicycle exercise. After 11 months of trimazosin treatment the mean casual blood pressure was reduced from 165/106 mm Hg to 147/92 mm Hg. The intra-arterial systolic and diastolic pressure was reduced by 3–7% at rest and during 50, 100 and 150 W exercise. Total peripheral resistance was reduced by 8–14% and cardiac output was slightly higher (2–8%) in all situations. Stroke volume and heart rate remained unchanged, as did body fluid volumes (isotope dilution) and body weight. Side effects were minor and transient. Thus, the haemodynamic responses to trimazosin are similar to but weaker than those of other alpha1-adrenoceptor blockers. The efficacy of the sustained-release formulation of trimazosin was low and daily doses above 600 mg are likely to be needed by many patients.
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  • 9
    ISSN: 1432-1041
    Keywords: Fibrinolysis ; hypertension ; atenolol ; doxazosin ; tissue plasminogen activator ; plasminogen activator inhibitor ; cholesterol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Disturbances in the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the fibrinolytic system have been evaluated. Eighty four subjects with previously untreated mild to moderate hypertension and elevated serum cholesterol were randomized to receive atenolol or doxazosin in a double-blind study over 6 months. Tissue plasminogen activator(tPA) and plasminogen activator inhibitor (PAI-1) were measured in citrated plasma samples before and after venous occlusion before and at the end of the study period. tPA activity after venous occlusion and tPA capacity were significantly increased after doxazosin as compared to pretreatment values. The fibrinolytic variables did not change in the atenolol group. Thus, doxazosin but not atenolol, improved the activity of the fibrinolytic system in patients with hypertension and an elevated serum cholesterol level. This effect of doxazosin warrants consideration when selecting a first-line antihypertensive drug.
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  • 10
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    European journal of clinical pharmacology 19 (1981), S. 19-24 
    ISSN: 1432-1041
    Keywords: hypertension ; guanfacine ; central antihypertensives ; withdrawal ; catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1. Guanfacine (2–6 mg/day) a centrally acting antihypertensive drug, was effective in controlling blood pressure in 5 essential hypertensives and lowered plasma noradrenaline and urinary catecholamine excretion. 2. Withdrawal of guanfacine by blind substitution of identical placebo tablets under observation in hospital led to a gradual recovery of blood pressure over 2–4 days. 3. Salivary flow, which was reduced on guanfacine, returned to pretreatment levels by 2 days after withdrawal and significantly exceeded control for the next two days. 4. Urinary catecholamine excretion returned to pretreatment levels by 3 days but did not exceed control levels during the period of study. 5. Plasma noradrenaline returned gradually to pretreatment levels, and by day 4 significantly exceeded them. 6. No patient experienced symptoms suggesting catecholamine excess although four out of five reported a headache from the second day onwards. 7. Guanfacine, a centrally acting drug which pharmacologically resembles clonidine, has a slow offset of hypotensive effect over 2–3 days. Symptoms or biochemical evidence of catecholamine excess were not encountered within 48 h of withdrawal, possibly reflecting the longer duration of action and plasma half-life of guanfacine.
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  • 11
    ISSN: 1432-1041
    Keywords: guanfacine ; methyldopa ; hypertension ; rebound hypertension ; withdrawal symptoms ; plasma noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nine patients with essential hypertension completed a clinical trial designed to study the effects and side effects of administration and withdrawal of guanfacine (2 mg tds) and methyldopa (250 mg tds) on blood pressure, heart rate, and plasma noradrenaline. The study was of randomised doubleblind crossover design with two active therapy phases of eight weeks each, preceded by an initial 4 week placebo phase, separated by an intermediate 2 week placebo phase, and followed by a final 2 week placebo phase. Patients took bendrofluazide 5 mgs daily throughout the entire trial, during both active and placebo periods. Each patient was admitted to hospital at the end of the 8 week active treatment phases, so that the effects of drug withdrawal on blood pressure, heart rate, plasma noradrenaline and side reactions, could be closely observed and monitored. The main conclusions from analysis of the results were that: 1. The hypotensive efficacy of guanfacine and methyldopa was very similar in the doses used, each of the two drugs lowering the supine mean arterial pressure by about 15 mm Hg and the supine diastolic pressure by about 10 mm Hg. 2. The frequency of side effects was greater with guanfacine than with methyldopa. 3. There was no signficant early rebound phenomenon after withdrawal of either methyldopa or guanfacine. 4. There was tendency for the blood pressure to rise slowly and marginally above initial placebo values, 2 weeks after cessation of guanfacine treatment though this was not significant. It was however, accompanied by a significant increase in plasma noradrenaline at 2 weeks. This was not seen 2 weeks after cessation of methyldopa. There was no single incidence of worrying rebound hypertension or withdrawal symptoms either early or late in any patient following cessation of methyldopa or guanfacine.
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  • 12
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    European journal of clinical pharmacology 20 (1981), S. 163-168 
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; cardiac output ; extracellular fluid volume ; renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of captopril 450 mg/day for 4 weeks on blood pressure, heart rate, cardiac output and extracellular fluid volume were compared in severe, often drug-resistant hypertension (n=23), mild to moderate hypertension associated with renal artery stenosis (n=10) and mild to moderate essential hypertension (n=20). Plasma renin in the three groups was 52±19, 58±17 and 20±4 µU/ml (mean ± SEM), respectively. Blood pressure fell by 18±4%, 21±2% and 18±1%. The pressure drop was mainly due to a fall in peripheral vascular resistance. Addition of the diuretic hydrochlorothiazide (25–100 mg/day) caused a further fall in resistance. Despite the vasodilator effect of captopril, reflex cardiostimulation and reactive fluid retention were not observed. In severe hypertension, captopril alone was more effective in lowering blood pressure than combined diuretic-betablocker-vasodilator therapy. Moreover, cardiac output in these patients was higher and resistance was lower after captopril than during combined treatment. Thus, captopril was capable of normalising the abnormal haemodynamic state in patients with essential hypertension, and in hypertension associated with renal artery stenosis. Despite marked differences in pre-treatment plasma renin, the effects of captopril on systemic haemodynamics were similar in all the patients.
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  • 13
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; haemodynamic effects ; renal plasma flow ; renal tubular function ; plasma renin activity ; aldosterone ; Ro 12-4713
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Selected cardiovascular and endocrine effects of the new oral vasodilator Ro 12-4713 have been evaluated in an acute single dose study. In five patients with essential hypertension, Ro 12-4713 caused a dose-dependent decrease in supine and upright blood pressure and an increase in heart rate. Initial effects occurred one to 2 h after drug ingestion and maximal effects were noted after five hours and persisted for at least 8 h. Blood pressure was normalized, and the antihypertensive and chronotropic effects persisted for 24 h after a dose of about 300 mg/1.73 m2. Plasma and urinary norepinephrine and plasma renin levels tended to be raised, whereas plasma and urinary epinephrine and plasma aldosterone did not change. Changes in supine heart rate were inversely correlated with changes in mean blood pressure (r=−0.60; P〈0.02), and positively with those in plasma norepinephrine (r=0.55; P〈0.05) and renin (r=0.62, P〈0.01); changes in supine plasma renin level were also inversely correlated with those in mean blood pressure (r=−0.65; P〈0.01), and positively with those in plasma norepinephrine (r=0.58; P〈0.05). 24 h-urinary sodium excretion was significantly (P〈0.001) decreased; it was positively correlated with mean blood pressure (r=0.51; P〈0.05) and inversely with supine plasma renin activity (r=−0.63; P〈0.01). In six normal subjects and six patients with essential hypertension, effective renal plasma flow and the renal clearance of sodium, potassium, calcium and uric acid were not significantly altered five hours after a dose of Ro 12-4713 of about 250 mg/1.73 m2; glomerular filtration rate tended to be slightly decreased, and filtration fraction was significantly (P〈0.05) reduced in the hypertensive patients. At the same time blood pressure was decreased and plasma norepinephrine (P〈0.01) and renin (ns) were slightly increased in both groups. Ro 12-4713 in a single oral dose of about 300 mg appeared to be a potent, long acting, hypotensive vasodilator.
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  • 14
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    European journal of clinical pharmacology 19 (1981), S. 25-32 
    ISSN: 1432-1041
    Keywords: clonidine ; hypertension ; baroreceptor reflex ; mode of action ; sympathetic activity ; urinary catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 ± 0.15 mg/day) alone in 13 essential hypertensive men, assessing several biochemical indices of sympathetic function, as well as physiologic parameters, including baroreflex sensitivity, the cold pressor test, and the hypotensive response to alpha adrenergic blockade. Clonidine diminished mean arterial pressure (from 104±5 to 84±3 mmHg;p〈0.01), without associated changes in several biochemical parameters of sympathetic outflow (urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid; allp〉0.1). Circulatory baroreflex function was not enhanced by clonidine, during either the amylnitrite test or the phenylephrine test, before or after parasympathetic blockade with atropine. The cold pressor test, an index of efferent sympathetic pressor function, was also unaltered. The enhanced mean arterial pressure response to phentolamine during clonidine therapy (from a fall of 14.8±4.3 to 39.4±5.2 mmHg,p〈0.01), suggested an increase in alpha adrenergic vascular tone, perhaps mediated by clonidine's alpha agonist properties in vascular smooth muscle. The antihypertensive mechanism of longterm low dose clonidine cannot reliably be ascribed either to baroreflex enhancement or to suppression of sympathetic outflow.
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  • 15
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    European journal of clinical pharmacology 19 (1981), S. 113-118 
    ISSN: 1432-1041
    Keywords: tolmesoxide ; vasodilators ; hypertension ; side-effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and a diuretic. After a 50 mg oral dose mean (± SD) peak plasma concentration of T was 1.13±0.29 µg/ml−1 and occurred 0.79±0.40 h after the dose; mean peak plasma concentration of its sulphone metabolite (M) was 0.37±0.09 µg/ml−1 at 1.92±1.32 h after the dose. Following peak plasma concentrations there was a monoexponential decline in T and M concentrations with half-lives of 2.78±0.77 h and 10.78±7.85 h respectively. There was a linear increase in plasma concentration of T and M during incremental dosing with 50–200 mg t. i. d. During in-patient administration of 600–900 mg T daily (n=6) there was no significant change in blood pressure, pulse rate or body weight. Out-patient administration of 900 mg T daily (n=4) was associated with a significant fall in mean systolic but not diastolic bp (lying −15/+1 mm Hg. standing −25/−8 mm Hg). A further fall was observed in 2 subjects receiving 1200 mg and 1500 mg daily. Supine pulse rate increased (mean ± SD) significantly from 55±5/min to 66±8/min following 900–1500 mg T in 4 out-patients. Severe nausea and other gastro-intestinal side-effects in all subjects receiving 600–900 mg daily eventually necessitated drug withdrawal. In its present from T is not recommended for the treatment of hypertension.
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  • 16
    ISSN: 1432-1041
    Keywords: carteolol ; hydrochlorthiazide ; amiloride ; hypertension ; double-blind clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of carteolol, a new β-blocking agent, added to basal diuretic treatment (hydrochlorthiazide 50 mg and amiloride 5 mg) has been assessed in a controlled trial in 17 patients with mild-to-moderate hypertension. The trial was divided into 4 stages: 1) run-in period with no antihypertensive treatment, 2) diuretic period (the diuretic being continued as basal treatment during the two following periods), 3) carteolol titration period, and 4) double-blind cross-over period comparing carteolol with placebo, which lasted 2 times 4 weeks. Although the diuretic effectively reduced the blood pressure, 17 of the 20 patients originally studied still had an elevated diastolic blood pressure (≧ 95 mmHg) after the diuretic period, thus fulfilling the inclusion criteria for the study. During the titration period carteolol 5 to 20 mg b. i. d. significantly reduced the elevated blood pressure. The blood pressure was reduced to normal in all 17 patients, although in two patients this occurred only during the double-blind period. During the double-blind period, the dose of carteolol was used which had given a satisfactory response during the titration period. The blood pressure in the 14 patients who completed the trial remained low both with carteolol and placebo during the double-blind stage, and was only slightly lower with carteolol than with placebo. This is probably due to a “carry-over” effect. Three patients discontinued the trial due to side effects (1 urticaria, 1 insomnia and 1 nausea) while on carteolol. There was no other difference between carteolol and placebo in the number or severity of side effects.
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  • 17
    ISSN: 1432-1041
    Keywords: vasodilator ; hypertension ; antihypertensive treatment ; catecholamines ; renin ; aldosterone ; blood volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive efficacy and endocrine profile of the new antihypertensive agent, Ro 12-4713, were evaluated in 23 patients (17 men and 6 women) with moderate to severe arterial hypertension. Following addition of Ro 12-4713 to pre-existing therapy with diuretics and beta-blockers or sympatholytics, blood pressure in most of the patients was normalized within one month by a daily dose of 60 to 120 mg. Heart rate was only slightly increased. Orthostatic hypotension was not observed. Weight gain or oedema formation occurred in 14 patients within the first four weeks, but could be controlled satisfactorily by intensified diuretic therapy. Increased hair growth occurred in most of the patients. After a mean duration of treatment of 2.8 months, plasma volume and plasma and urine sodium were unaltered, and plasma potassium was slightly decreased. Plasma renin activity was doubled, whereas plasma aldosterone concentrations were unaltered. Plasma norepinephrine levels were high before and increased only slightly during chronic Ro 12-4713 treatment, whereas urinary norepinephrine excretion was unchanged. Plasma and urinary epinephrine were unaltered by Ro 12-4713. Ro 12-4713 appears to be a potent vasodilator for the combination treatment of hypertension in men.
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  • 18
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    European journal of clinical pharmacology 20 (1981), S. 335-338 
    ISSN: 1432-1041
    Keywords: atenolol ; atherosclerosis ; hypertension ; serum lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Serum lipoproteins were determined in 15 patients before and during antihypertensive treatment with atenolol 0.1–0.2 g/day for a mean of 8 months. The mean blood pressure fell from 171/103 to 154/93 mm Hg (p〈0.05). Significant lipoprotein changes were an increase in very low density triglycerides (VLDL-TG) from 1.21±0.95 (SD) to 1.62±1.24 mmol/l (p〈0.01) and in low density (LDL) TG from 0.46±0.12 to 0.51±0.12 mmol/l (p〈0.05). Together, these TG increases resulted in development of hypertriglyceridaemia in 7/15 patients during atenolol treatment. No effect on whole serum cholesterol or on the high density lipoprotein cholesterol concentrations were found. Thus, some patients on long term treatment with atenolol seem to receive the benefit of normotension at the cost of hypertriglyceridaemia. This may have practical implications, since hypertriglyceridaemia constitutes an important risk factor for atherosclerosis.
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  • 19
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    European journal of clinical pharmacology 20 (1981), S. 347-349 
    ISSN: 1432-1041
    Keywords: reserpine ; syrosingopine ; prolactin secretion ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 20 mild hypertensive women, reserpine induced a significant increase in mean plasma PRL, both under basal conditions (from 6.6±0.9 to 17.9±2.9 ng/ml), and on repeated determinations during the day. In contrast to reserpine, the administration of syrosingopine, a synthetic compound derived from reserpine, to the same subjects was not followed by a significant change in prolactin level. Beyond their pharmacological interest, these results are of clinical importance when considering that rauwolfia alkaloids are used for long term treatment, and that an increase in PRL levels is important in pathology, both in relation to the function of the hypophyseogonadal axis and in view of its possible facilitation of the growth and development of mammary cancer.
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  • 20
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    European journal of clinical pharmacology 38 (1990), S. S139 
    ISSN: 1432-1041
    Keywords: carvedilol ; serum lipid metabolism ; hypertension ; normotension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of carvedilol (an α · β-blocker) on lipid metabolism were assessed in addition to its hypotensive effect. The subjects were 18 men and 18 women, 20 with hypertension and 16 normotensives with other conditions requiring carvedilol treatment. They were aged from 31 to 79 years and were given a daily dose of 5–20 mg carvedilol (average, 9.7 mg/day) for 12 weeks. Significant falls were seen in blood pressure and heart rate after 12 weeks in the hypertensive subjects (mean ± SE) (systolic: from 164 ± 2 to 141 ± 2 mm Hg,P 〈 0.001; diastolic: from 98 ± 1 to 85 ± 2 mm Hg,P 〈 0.001; heart rate: from 71 to 65 beats/min,P 〈 0.001). Smaller changes in blood pressure and heart rate were seen in the normotensive subjects, with the fall in systolic pressure being significant (from 143±3 to 135 ± 2 mm Hg,P 〈 0.01). There were no significant changes in the overall serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and phospholipid levels. In the subgroup with a pretreatment serum triglyceride level of 〉 150 mg/dl, a significant fall of 52.1 mg/dl was seen (P 〈 0.05). Lipoprotein analysis showed a significant fall in α-lipoprotein levels (P 〈 0.05). The atherogenic index did not change significantly, and it was concluded that carvedilol was an effective antihypertensive agent that produced no adverse effects and possibly had beneficial effects on lipid metabolism.
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  • 21
    ISSN: 1432-1041
    Keywords: hypertension ; combination treatment ; hydrochlorothiazide ; carvedilol ; atenolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carvedilol [25 mg once daily] (o. d.) was compared to atenolol (50 mg o. d.) as an adjunct to pre-existing hydrochlorothiazide (HCTZ) monotherapy in patients with mild to moderate hypertension [diastolic blood pressure (DBP),100–115 mm Hg]. After a placebo run-in phase of 2 weeks, 131 patients received 25 mg HCTZ o. d. for 4 weeks. In all, 122 patients were transferred to the double-blind phase, in which 25 mg carvedilol or 50 mg atenolol was randomly added to HCTZ. After an additional 6 weeks of treatment, 112 patients were evaluable for efficacy (C/HCTZ group,n = 54; A/HCTZ group,n = 58). Blood pressure was measured and the heart rate was counted before medication, at 2-week intervals throughout the trial, and 2 h after medication on the 1st and the last day of the combination treatment period. Serum lipids were measured in addition to routine laboratory variables. A therapeutic response was defined as a reduction in supine and standing diastolic blood pressure to values of 〈 90 mmHg. In a relatively low number of patients (6 of 131), a response as defined above was achieved with HCTZ alone. This may be accounted for by the fact that patients were required to have a diastolic blood pressure of at least 100 mgHg and by the relatively short period of monotherapy. The two groups of patients receiving different combination treatments were well matched for demographic data and blood pressure values before the adjunct was added. In both groups there was a marked additional blood pressure decrease on the initiation of combined treatment. At the end of the study the medians of all blood pressure values were well within normal ranges, which was not the case with HCTZ alone. On the last day of the trial, the responders comprised 67% of the C/HCTZ group and 71% of the A/HCTZ group. No relevant changes in lipid values were observed with combination treatment vs diuretic monotherapy. No serious adverse event attributable to one of the study drugs was reported. The results of the present trial suggest that the antihypertensive efficacy of both combinations is superior to that of HCTZ alone and that there is no difference in efficacy between the two combinations. Adding carvedilol or atenolol to pre-existing HCTZ appears to be safe. The tolerability of the antihypertensive treatment does not seem to decline, despite considerable additional decreases in blood pressure.
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  • 22
    ISSN: 1432-1041
    Keywords: Verapamil ; renal replacement therapy ; hypertension ; pharmakokinetics ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-eight hypertensive patients on renal replacement therapy (HD, HF, PD) were treated with verapamil (Isoptin RR-slow release) in an open label study. Blood pressure was satisfactorily reduced in 21 patients (84%). Due to adverse reactions the treatment had to be discontinued in 4 patients. Verapamil clearances were calculated according to different dialysis methods. No changes in dose or mode of application of verapamil were necessary using any mode of renal replacement therapy.
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  • 23
    ISSN: 1432-1041
    Keywords: hypertension ; verapamil haemodynamics ; atrial natriuretic peptide ; elderly ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effect of the calcium-antagonist verapamil was investigated in two groups of patients, adult hypertensives (AH, 〈 65 years of age) and elderly hypertensives (EH, 〉 65 years of age), who were treated with 240 mg p. o. sustained-release (SR) verapamil for 4 months. Arterial blood pressure was significantly reduced in both groups: the responders' rate was 65% in the AH group and 82% in the EG group. The heart rate was slightly but not significantly reduced. An improvement in cardiac haemodynamics was observed [cardiac index (CI), from 3.00 ± 0.51 to 3.25 ± 0.83 ml min−1 m−2 in AH and from 2.35 ± 1.08 to 3.04 ± 0.86 ml min−1 m−2 in EG]. We also evaluated the plasma concentrations of atrial natriuretic peptide (ANP) before and after treatment; ANP levels increased significantly only in the EH group. No serious side effects occurred. In conclusion, verapamil SR provided effective and well-tolerated antihypertensive treatment in both adult and elderly patients.
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  • 24
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    European journal of clinical pharmacology 39 (1990), S. 539-543 
    ISSN: 1432-1041
    Keywords: Felodipine ; hypertension ; vasodilator ; haemodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sixteen patients with previously untreated mild/moderate hypertension (WHO Stage I) were studied: 7 women and 9 men, mean age 56.2 y. Haemodynamics, central and pulmonary blood volumes were measured by radionuclide techniques and repeated after 8 weeks felodipine therapy. To achieve a target diastolic blood pressure of 〈 95 mm Hg 12 patients required 5 mg bid, 2 10 mg bid and 1 2.5 mg bid; 1 withdrew after 2 weeks. Mean (SD) arterial blood pressure (mm Hg) was 189/106 before, and 182/103 after 2 weeks placebo treatment and fell to 148/84 after 8 weeks felodipine therapy. Relative systemic vascular resistance fell by 19% from 2146 to 1734 dyn.s.cm−5. There were no significant changes in heart rate, cardiac index, total blood volume, pulmonary blood volume or left ventricular ejection fraction. Plasma renin activity did not rise significantly. Short lived vasodilator side effects occurred in 7/16 patients during initial treatment and mild ankle oedema persisted in 4/16 patients. In contrast to the haemodynamic changes seen acutely with felodipine, the only sustained changes after 8 weeks therapy are reductions in systemic vascular resistance and blood pressure.
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  • 25
    ISSN: 1432-1041
    Keywords: Captopril ; Diabetes ; nephropathy ; hypertension ; glucose tolerance ; plasma lipids ; blood pressure ; long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of the angiotensin converting enzyme inhibitor captopril on blood pressure, proteinuria, creatinine clearance and metabolic control in diabetic nephropathy have been evaluated. Captopril 144 mg per day was given to 8 longstanding, insulin-dependent, diabetic females with nephropathy. The blood pressure was significantly reduced (systolic 45.4, diastolic pressure 30.6 and mean arterial pressure 33.8 mm Hg after 24 weeks of treatment). Plasma renin activity rose significantly from a basal value of 1.60 to 6.71 ng·ml−1·h−1, and so did serum potassium (from 4.57 to 4.83 mEq·l−1). Serum aldosterone fell from 161 to 70.9 pgm·ml−1 and from 27.3 to 15.3 μg·24 h−1 in plasma and urine, respectively, after 6 months on captopril therapy. Urinary protein excretion was decreased by about 48% and creatinine clearance remained unchanged throughout the study. Plasma triglycerides and cholesterol also remained unchanged, and glycosylated haemoglobin was significantly reduced from 13.8 to 10.2% after captopril. The results suggest that captopril is a useful drug to treat hypertension in patients suffering from diabetic nephropathy, as the decline in kidney function can be reduced without impairing glucose tolerance or the lipid profile.
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  • 26
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    European journal of clinical pharmacology 19 (1981), S. 395-401 
    ISSN: 1432-1041
    Keywords: sotalol ; hydrochlorothiazide ; hypertension ; combination fixed ratio ; serum potassium ; long term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The combination of sotalol and hydrochlorothiazide in a fixed ratio of 6.4:1 was evaluated in thirty patients with uncomplicated hypertension. In the first part of the study, once daily administration of an optimal dose of the combination was significantly more effective than either hydrochlorothiazide or sotalol alone in lowering both the supine and standing systolic and diastolic blood pressure. Blood pressure was still controlled 24 h after the previous dose. Serum potassium fell by 0.37 mEq/l from the mean pretreatment value after treatment with the combination, but it still remained within the normal range. In the second part of the study the long term effect of the combination on blood pressure, heart rate and biochemical parameters was studied in twenty patients. Supine and standing blood pressure fell by 28.7/15.3 mmHg and 29.5/17.6 mmHg, respectively (p〈0.001). Serum potassium was 3.98±0.07 mEq/l after twelve months of therapy; potassium supplements were not administered. Like serum potassium, the other biochemical parameters remained within the normal range. The combination was well tolerated on long term use, and only one patient withdrew from the study.
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  • 27
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    European journal of clinical pharmacology 20 (1981), S. 1-8 
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; angiotensin ; renin ; aldosterone ; catecholamines ; prostaglandins ; kininase II ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute hypotensive effect of captopril 25 mg was investigated in 26 hypertensive patients (11 with essential and 15 with renal arterial disease). Intra-arterial blood pressure was recorded continuously and arterial blood was sampled for renin, angiotensin I and II, aldosterone, kininase II, catecholamines and prostaglandins. Captopril led to an increase in plasma renin activity, active and total plasma renin concentration and angiotensin I, a decrease in plasma kininase II activity, angiotensin II, aldosterone, prostaglandins E2 and F2* and no change in plasma (nor)adrenaline, dopamine and inactive renin concentration. The hypotensive effect of captopril was related to the changes in plasma angiotensin II level and inversely to the change in prostaglandin E2; the correlation coefficients were low, respectively 0.61 and −0.44. It is likely that the acute hypotensive effect of captopril to some extent is related to changes in plasma angiotensin II and in prostaglandins E2 and F2*. There is no evidence for a role of the adrenergic systems in the hypotensive response.
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  • 28
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    European journal of clinical pharmacology 20 (1981), S. 399-405 
    ISSN: 1432-1041
    Keywords: alpha-adrenergic blocker ; hypertension ; blood pressure ; pulse rate ; noradrenaline ; plasma renin activity ; plasma aldosterone ; dopamine-beta-hydroxylase ; E-643
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To determine whether E-643, a new α-blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine-β-hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 → 151±28/89±14 mmHg), sitting (158±22/101±11 → 138±28/89±15 mmHg) and standing (153±32/103±21 → 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 → 69±10 beats/min), but was increased in the sitting (68±10 → 73±9 beats/min) and standing (73±10 → 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine-β-hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine-β-hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.
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  • 29
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    European journal of clinical pharmacology 20 (1981), S. 407-411 
    ISSN: 1432-1041
    Keywords: chlorthalidone ; hypertension ; dose response
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The dose response curve for 25, 50, 75 and 100 mg doses of chlorthalidone was studied in double blind fashion over an 8 week period in patients who presented with untreated mild hypertension. One hundred and thirty four patients completed this multicentre, family practice study. After 2 week's medication, a decline in blood pressure was noted in all dosage groups and this was maximal by 4 weeks. At 8 weeks all doses of chlorthalidone induced a significant reduction in both systolic and diastolic blood pressures (mean −18 and −10 mmHg respectively). Amongst the 4 dosage groups, no differences in response were noted resulting in a flat dose response curve. During the study, mean blood urea and serum uric acid rose whilst serum potassium fell, the urea and potassium being least affected in the 25 mg dosage group. As the dosage of chlorthalidone increased, so the tendency for abnormal laboratory values increased. Unwanted effects sought during the study were relatively few in number. No clear dose response relationship was evident although the positive responses in the 25 mg dosage group were less than in the higher dosages. These results suggest that 25 mg chlorthalidone is the optimum dosage for initiation of therapy in patients with mild to moderate hypertension. This dosage is associated with less adverse biochemical changes and unwanted effects than the higher dosages studied.
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  • 30
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    European journal of clinical pharmacology 20 (1981), S. 453-457 
    ISSN: 1432-1041
    Keywords: diuretics ; trichlormethiazide ; hypertension ; pharmacokinetics ; renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of trichlormethiazide (TCZ) was studied in twelve patients after a single 4 mg dose. Seven patients had normal renal function with creatinine clearances greater than 90 ml/min. Five patients had compromised renal function with creatinine clearances averaging 48±29 ml/min. The TCZ plasma half life and area under the plasma concentration-time curve (AUC) were significantly greater in patients with impaired function, compared to patients with normal renal function. There were no significant differences between the two patient groups in terms of either rate of drug absorption or total urinary recovery of unchanged drug. Furthermore, there was no correlation between peak drug levels or AUC and renal excretion of water or electrolytes.
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  • 31
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    European journal of clinical pharmacology 21 (1981), S. 1-8 
    ISSN: 1432-1041
    Keywords: hypertension ; combination therapy ; population survey ; drug treatment ; prescription patterns ; population incidence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a cross-sectional study, antihypertensive drug treatment was studied in a representative population sample of people aged 30–64 years, using a combination of postal survey, personal interview, clinical assessment and drug prescriptions. 11% of the men and 16% of the women were currently taking antihypertensives; 54% of patients used one, 38% used two, and 8% used three or more preparations. Men used slightly more drugs than women. Diuretics were used by 62% and betablockers by 49% of the sample population. Fixed combinations of thiazides and potassium-sparing agents formed 70% of all diuretic preparations used. Only 12% of the patients used fixed antihypertensive combinations, of which over half were diuretic-reserpine-vasodilator combinations; women and older patients used them most often. The most common freely combined preparations were diuretics and betablockers, which formed almost half of all two-drug combinations, and were also present in 70% of all triple combinations. Adequate control of blood pressure (DBP 〈100 mmHg) was achieved by slightly under 50% of the patients, the BP of women being more adequately controlled than that of men. Differences in BP control were found between the different drugs and combinations. Antihypertensive combination therapy is important in successful treatment, but we still cannot be sure whether fixed combination preparations or, as in this study, free combinations of marketed preparations are better alternatives for treatment.
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  • 32
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    European journal of clinical pharmacology 21 (1981), S. 87-92 
    ISSN: 1432-1041
    Keywords: hypertension ; metoprolol ; sotalol ; comparison ; plasma levels ; serum uric acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 28 patients, aged 35–62 years, with uncomplicated hypertension, entered a double-blind, crossover study, in which the effects of single daily doses of sotalol and metoprolol were compared. Both drugs exerted a clinically useful anti-hypertensive effect as monotherapy, or in combination with a thiazide diuretic. No significant difference in hypotensive effects was noted between the two beta-blocking agents, when the dose was titrated to an optimal clinical effect. Treatment with sotalol and metoprolol was associated with a clinically insignificant increase in serum uric acid concentration. The side-effects observed were few, and in only two cases was therapy discontinued. We regard both sotalol and metoprolol as useful anti-hypertensive drugs.
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  • 33
    ISSN: 1432-1041
    Keywords: frusemide ; saralasin ; hypertension ; reninangiotensin ; sodium ; diet
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The use of tests of the renin-angiotensin system for predicting antihypertensive responses to frusemide combined with dietary sodium deprivation was evaluated in eighteen patients with severe hypertension. No relationship could be shown between changes in blood pressure induced by the angiotensin analogue, saralasin, and the short-term or long-term therapeutic effects of diuretic- and diet-induced sodium depletion. Mean values for saralasin response and initial plasma renin activity in eight patients whose blood pressure was adequately controlled by therapeutic sodium depletion were closely similar to those obtained in the remaining ten patients, who proved refractory to this treatment.
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  • 34
    ISSN: 1432-1041
    Keywords: cicletanine ; bendrofluazide ; hypertension ; urinary electrolytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute effects on urinary electrolyte excretion and plasma potassium were compared of the anti-hypertensive dihydrofuropyridine cicletanine with the thiazide bendrofluazide in 6 patients with uncomplicated essential hypertension. Cicletanine 50 mg or 100 mg and bendrofluazide 5 mg caused no acute decrease in blood pressure compared to placebo for 24 h after treatment. In the 24 h after a single dose of cicletanine 50 mg there was no increase in urinary sodium, potassium or volume compared to placebo. After a single dose of cicletanine 100 mg there was a significant increase in 2 h urinary sodium excretion compared to cicletanine 50 mg and in the first 6 h a significant increase in urinary potassium compared to placebo. Urine volume did not change significantly. After bendrofluazide 5 mg urinary sodium excretion increased significantly in the first 6 h as well as in the subsequent 18 h compared to placebo and both cicletanine 50 mg and 100 mg. Urinary potassium excretion was also significantly increased in the first 6 h after bendrofluazide compared to placebo, and urine volume significantly increased from 6 to 24 h after bendrofluazide 5 mg compared to placebo and cicletanine 100 mg. Plasma potassium was significantly reduced and plasma renin activity significantly increased 24 h after bendrofluazide 5 mg but these measurements were not significantly different from placebo after cicletanine 50 or 100 mg. These results suggest that cicletanine 100 mg has milder acute natriuretic effects than the thiazide bendrofluazide 5 mg. In contrast cicletanine 50 mg is associated with no major acute renal effects. In view of evidence that with long-term treatment both cicletanine 50 and 100 mg have anti-hypertensive effects, these findings suggest that cicletanine may act by a different mechanism in lowering blood pressure at low and high dose.
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  • 35
    ISSN: 1432-1041
    Keywords: Cadralazine ; hypertension ; prazosin ; metoprolol ; combined therapy ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A randomized multicentre between-patient study comparison has been made of the efficacy and tolerability of cadralazine and prazosin, both administered for 6 weeks to hypertensive patients with a supine diastolic blood pressure (DBP) ≥ 95 mm Hg whilst on a beta-adrenoceptor-blocker. The doses of the beta-adrenoceptor-blocker (metoprolol SR 200 mg once daily) and cadralazine (10 mg once daily) were held constant during the study, while prazosin was individually titrated from 0.5 mg to a maximum of 2 mg tds. 108 patients (50 m and 58 f; mean age 54 y) were enrolled in 12 centres. Twelve patients withdrew due to adverse effects or poor efficacy (5 patients on prazosin and 7 on cadralazine). Both treatments induced a similar significant reduction in systolic blood pressure (SBP) and DBP, allowing normalization of BP in 58% of subjects on cadralazine and 55% on prazosin. Heart Rate (hR) increased significantly from 67 to 72 beats · min−1 in those on cadralazine and from 65 to 69 beats · min−1 on prazosin. Body weight was unchanged. Adverse effects were mild and typical of vasodilators, such as headache, flushing and dizziness. Physician evaluation of drug efficacy was not different between drugs, and cadralazine was rated better in terms of tolerability. Thus, in this multicentre study, cadralazine in the fixed dose of 10 mg once daily, as a second-step antihypertensive treatment in patients not satisfactorily controlled by a beta-adrenoceptor-blocker, was as effective and showed a similar side effect profile to prazosin given three times daily.
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  • 36
    ISSN: 1432-1041
    Keywords: hypertension ; captopril ; nifedipine ; plasma renin activity ; aldosterone ; vasopressin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a single-dose crossover study Captopril (SQ 14225), 1 mg/kg body weight, and Nifedipine (Bay a 1040) 20 mg were administered orally to 12 hospitalized patients with essential hypertension (Stage 1 or 2, W. H. O.). Both drugs significantly reduced blood pressure, but each dose acted differently: the mean maximum arterial pressure reduction was faster and greater with Nifedipine than with Captopril: −23±2% at 37±15 min and −17±1% at 86±25 min, respectively. Captopril inhibited angiotensin II and aldosterone production, but did not accelerate heart rate or stimulate vasopressin release. Nifedipine stimulated vasopressin release and increased heart rate, but the renin angiotensin aldosterone system was not significantly affected. The blood pressure reduction was related to the initial level of activation of the renin angiotensin system only for Captopril. The blood pressure reduction induced by one drug was not related to that produced by the other in the same patient.
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  • 37
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    European journal of clinical pharmacology 20 (1981), S. 237-240 
    ISSN: 1432-1041
    Keywords: labetalol ; clonidine ; hypertension ; adverse effects ; plasma catecholamines ; plasma cAMP ; withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven hypertensive patients in whom clonidine therapy had to be discontinued, were treated prophylactically with labetalol, in order to avoid a possible hypertensive crisis. Most of the known side effects, which are consistent with the withdrawal phenomenon were observed, e.g. tremor, insomnia and apprehension, but headaches and flushing did not occur. Blood pressure levels remained unchanged, despite up to a 20-fold increase in plasma catecholamines. The lack of change in serial measurements of plasma cyclic AMP level appears to indicate that adequate adrenergic blockade was induced by labetalol. Since labetalol is a potent anti-hypertensive drug, and is also effective in avoiding a possible hypertensive crisis due to withdrawal of clonidine, we propose to use it as the drug of choice whenever discontinuation of clonidine therapy is indicated.
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  • 38
    ISSN: 1432-1041
    Keywords: aldosterone ; hypertension ; propranolol ; blood pressure ; plasma level ; renin ; urine level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg×4 (Group 1), 80 mg×4 (Group 2) and 160 mg×4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h urinary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradually increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treatment. The maximum reduction in diastolic BP occurred after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduction was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA and PAC fell in all groups, and remained reduced during C and D in Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin-aldosterone system was initially suppressed in all groups, but for unknown reasons it increased towards the control level after seven to eleven weeks of therapy with 320 and 640 mg/day, and that the reduction in systolic BP increased with higher doses of propranolol and with increasing urinary propranolol excretion.
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  • 39
    ISSN: 1432-1041
    Keywords: clonidine ; minoxidil ; hypertension ; sympathetic nervous activity ; plasma renin activity ; cardiovascular responses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of clonidine and minoxidil on sympathetic nervous activity has been studied in 10 patients with accelerated or resistant hypertension. Clonidine 150 to 900 µg/day caused a significant decrease in blood pressure of 18.6 mm Hg, of heart rate 16.4 beats/min, or plasma renin activity 1.13 ng/ml·h, and of urinary noradrenaline excretion 11.55 µg/day, and a significant lengthening of the pre-ejection period of 12.4 ms. Minoxidil 5 to 22.5 mg/day caused a further significant decrease in blood pressure of 24.2 mm Hg, and significant increases in heart rate 8.2 beats/min, plasma renin activity 1.68 ng/ml·h, and of urinary noradrenaline excretion 5.0 µg/day, and a significant shortening of the pre-ejection period of 20.6 ms. Neither clonidine nor minoxidil altered plasma dopamine β-hydroxylase activity or the cardiovascular responses to treadmill exercise. It is concluded that clonidine is a useful alternative agent to block a minoxidil-induced increase in sympathetic nervous activity.
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  • 40
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    European journal of clinical pharmacology 21 (1981), S. 93-96 
    ISSN: 1432-1041
    Keywords: atenolol ; penbutolol ; hypertension ; beta-blockers ; intrinsic sympathomimetic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Atenolol 100 mg and penbutolol 40 mg given once a day were both effective in controlling moderate hypertension, as judged by a randomised controlled, double-blind trial in 45 patients treated for six weeks. Both drugs significantly reduced the resting supine and erect blood pressures. No serious adverse effects could be attributed to either drug. Bradycardia occurred more frequently with atenolol than with penbutolol. Penbutolol, which possesses intrinsic sympathomimetic activity, may be useful in the treatment of patients in whom some other beta-blocker has failed to bring about adequate control of the blood pressure, despite marked bradycardia.
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  • 41
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    European journal of clinical pharmacology 38 (1990), S. 359-361 
    ISSN: 1432-1041
    Keywords: urinary zinc ; captopril ; furosemide ; hydrochlorothiazide ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary zinc/creatinine ratio has been measured in five groups of patients with essential hypertension and in a group of healthy controls. The first four groups of patients consisted of subjects being treated for at least three months with captopril alone, hydrochlorothiazide alone, captopril plus hydrochlorothiazide, or captopril and furosemide. The fifth group comprised hypertensive patients not on any medication. The first four patient groups exhibited significantly increased urinary zinc/creatinine ratios when compared to the control and untreated hypertensive groups, but in the two combination regimens there was little zincuria. It is suggested that both diuretics inactivate the zincuric effect of captopril by binding to its sulphhydryl group within the tubular lumen.
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  • 42
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    European journal of clinical pharmacology 38 (1990), S. S134 
    ISSN: 1432-1041
    Keywords: hypertension ; physiologic effects ; diuretics ; vasodilators ; beta-blockers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Various antihypertensive drugs reduce blood pressure by different mechanisms. In some instances, adverse reactions occur because of specific hemodynamic effects. Examples include syncope with alpha-blockade or vasodilator therapy; fatigue or exercise intolerance with the reduction in cardiac output following the use of beta-adrenergic inhibitors; edema, headaches, or dizziness with the use of vasodilators such as calcium entry blockers; renal failure in patients with renal artery stenosis or renal insufficiency following the use of ACE inhibitors; and marked hyponatremia with volume depletion following the use of diuretics, especially in elderly patients. In the majority of patients, however, blood pressure lowering can be achieved without significant adverse effects. Combining small doses of different agents with different hemodynamic actions often results in good blood pressure control and minimal reactions. Examples of these include diuretics and beta-adrenergic inhibitors, diuretics and ACE inhibitors, and beta-blockers and vasodilators.
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  • 43
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    European journal of clinical pharmacology 38 (1990), S. S129 
    ISSN: 1432-1041
    Keywords: carvedilol ; metoprolol ; pindolol ; nitrendipine ; hypertension ; vasodilator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Carvedilol, a β-blocking drug with vasodilator activity, has been used in 4 studies in 107 elderly patients with essential hypertension and has reduced blood pressure effectively. In the first study the pharmacokinetics and clinical response were compared between 21 patients 〉 65 years of age and 8 patients aged 35–50 years). The peak blood levels, time to maximal concentration, area under the curve, half-life and trough level of the drug with chronic administration did not differ. The clinical responses to the drug were similar, with a greater fall in systolic blood pressure in the older group. However the initial systolic blood pressure in the older group was higher. Carvedilol was compared with metoprolol, pindolol and nitrendipine in elderly patients. The responses to carvedilol were at least equal to those obtained with the other drugs. Control was achieved in the three studies with once-daily therapy. There was no significant postural hypotensive effect. A feature of all studies was the large number of patients who responded to carvedilol. The side-effect profile of the drug was acceptable; headache and dizziness were more common than with placebo or the comparison drugs and were frequently associated. There were no adverse biochemical effects and the lipid profile was not altered. Carvedilol is an effective antihypertensive drug that lowers blood pressure equally well in the young and the old.
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  • 44
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    European journal of clinical pharmacology 40 (1991), S. 67-70 
    ISSN: 1432-1041
    Keywords: Dilevalol ; oxprenolol ; hypertension ; emotional stress ; haemodynamic changes
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of a single dose of 200 mg dilevalol, β-adrenoceptor blocker with additional vasodilating properties, and 200 mg oxprenolol on haemodynamic changes induced by emotional stress have been compared in 12 male young Caucasian patients with newly diagnosed labile hypertension. No difference was noted in the stress-induced increase of total peripheral resistance (TPR) following administration of the two substances (11% versus 6%). However, dilevalol revealed a vasodilating action by decreasing TPR at rest (from 1004 to 951 dyn·s·cm−5) and diastolic blood pressure (BP) (from 87 to 75 mm Hg) whereas TPR at rest remained unchanged after the intake of oxprenolol.
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  • 45
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    European journal of clinical pharmacology 38 (1990), S. 11-15 
    ISSN: 1432-1041
    Keywords: nisoldipine congestive heart failure ; haemodynamic effect blood pressure plasma renin activity ; plasma norepinephrine ; hypertension ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continous infusion of 0.2 μg · kg−1 · min−1. Haemodynamic measurements were performed at baseline and after 30 min. The mean arterial pressure fell from 91 to 73 mm Hg, pulmonary capillary wedge pressure from 31 to 26 mm Hg and systemic vascular resistance from 1695 to 1040 dyn · s · cm−5. The cardiac index (2.2 to 2.71 · min−1 · m−2, and stroke volume index (25 to 33 ml · m−2) were markedly increased. There was no reflex tachycardia as the heart rate dropped from 92 to 85 beats · min−1. Plasma renin activity and norepinephrine concentration did not change significantly. The findings indicate that nisoldipine acts as a strong vasodilator and that it has a beneficial acute haemodynamic effect in patients with severe left heart failure irrespective of its aetiology.
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  • 46
    ISSN: 1432-1041
    Keywords: nicardipine ; diabetic nephropathy ; calcium antagonist ; hypertension ; renal function ; albuminuria
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal effects of oral maintenance doses of nicardipine 60–120 mg/day have been studied in 18 hypertensive patients with Type 2 (non-insulin-dependent) diabetes mellitus: 6 with normoalbuminuria (urinary albumin excretion rate, AER 〈20 μg · min−1, Group A); 6 with incipient nephropathy, (AER 20–200 μg · min−1, Group B); and 6 with overt nephropathy (AER 〉200 μg · min−1, Group C). Treatment for 4 weeks significantly lowered the systolic and diastolic blood pressures and reduced total renal vascular resistance in all three groups. Nicardipine increased renal blood flow significantly in Group C and slightly in Group B, and had no effect in Group A. Glomerular filtration rate remained unchanged in all three groups. It significantly reduced AER and the fractional clearance of albumin in Group B, whereas AER in Groups A and C was not altered. Plasma renin activity, aldosterone concentration, osmotic pressure, serum total protein and albumin concentrations and haemoglobin A1c level were similar in the control and nicardipine phases in all three groups. The results suggest that nicardipine may preserve renal function whilst having a concomitant hypotensive action in hypertensive Type 2 diabetic patients with normoalbuminuria and incipient nephropathy, and that the drug may improve renal blood flow in patients with overt nephropathy. The effect of the drug on urinary albumin excretion may deserve further investigation.
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  • 47
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    Keywords: nifedipine ; hypertension ; lipids ; platelet aggregation
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of 6 weeks of nifedipine 30–60 mg/d on platelet aggregation and lipid parameters has been studied. A diminution in ADP-, adrenaline- and collagen-induced aggregation was observed. In the case of adrenaline-and collagen-stimulated aggregation the decrease was statistically significant. It was found that platelets which aggregated markedly during the placebo treatment were most strongly inhibited by nifedipine. The changes in lipid parameters were not significantly correlated with changes in aggregation.
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  • 48
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    European journal of clinical pharmacology 38 (1990), S. 17-20 
    ISSN: 1432-1041
    Keywords: nifedipine ; hypertension ; concentration-effect relationship ; individual dose ; side effects
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten patients with essential hypertension (WHO grade I–II) were treated in an open dose-adjustment study with the standard regimen of slow-release nifedipine 20 mg b. d. for 2 weeks and with an individualized dose for 6 weeks. The optimum dose, defined as that producing a pre-dose diastolic blood pressure (dBP) of 90 mm Hg at steady state, was determined from the individual concentration-effect relationship after a test-dose of 20 mg. On standard therapy, the reduction in pre-dose dBP was inadequate in 4 patients and it was excessive in 1 patient. After 2 weeks of individualized treatment, the required pre-dose antihypertensive effect was obtained in all patients. The individual doses required were 10 mg b. d., 10 mg t. d. s. 20 mg b. d., 20 mg t. d. s. and 20 mg q. d. s. One patient dropped out of the study because of side effects. Loss of the antihypertensive effect was observed in one patient after 6 weeks of treatment. On the optimized dose, the average value of the pre-and 2 h post-dose steady state nifedipine concentrations (27.6 μg/l) compared well with model-derived optimum concentrations (28.6 μl/l) (r=0.9210). The results show that the dose of nifedipine can be accurately predicted using the individual concentration-effect relationship after a single dose.
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  • 49
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    European journal of clinical pharmacology 38 (1990), S. 21-24 
    ISSN: 1432-1041
    Keywords: bisoprolol ; atenolol ; hypertension ; pharmacokinetics
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have compared the efficacy and pharmacokinetics of bisoprolol, a new cardioselective beta-adrenoceptor antagonist, with atenolol in a randomized double-blind crossover study in 12 patients (mean age 53.5 y) with mild to moderate essential hypertension. After a two week placebo wash-out period without any antihypertensive therapy, the patients were given bisoprolol 10 mg daily or atenolol 50 mg daily, increasing to 20 mg or 100 mg respectively if the sitting diastolic blood pressure did not fall below 90 mm Hg after two weeks of therapy. Crossover occurred after six weeks of active therapy followed by two weeks of placebo wash-out. After 6 weeks of therapy both drugs significantly reduced sitting and standing diastolic blood pressures (bisoprolol by 15% and 16% respectively, atenolo by 11% in both cases). However, while sitting and standing systolic pressures were significantly reduced by bisoprolol (13% and 16% respectively), only standing systolic pressures were significantly reduced by atenolol (11%), and this reduction was significantly less than with bisoprolol (p〈0.05). Both drugs similarly reduced mean sitting and standing heart rates. There were no significant differences between the single-dose and steady-state kinetics of either bisoprolol or atenolol. The mean plasma elimination half-life (t1/2) increased from 12.9 to 13.2 h during steady state on bisoprolol and from 7.2 to 11.5 h on atenolol. The apparent volume of distribution (Vz) was greater for bisoprolol than for atenolol after single dosing (235 1 vs 146 1) and at steady state (216 1 vs 137 1), but clearances were similar for both drugs. The maximum plasma concentration (Cmax) of bisoprolol increased from 45 μg·l−1 to 72 μg·l−1 during steady state and the Cmax of atenolol increased from 321 μg·l−1 to 410 μg·l−1 Adverse effects occurred in only one patient (lethargy while taking atenolol). These results suggest that bisoprolol has similar efficacy, safety, and pharmacokinetics to atenolol in patients with mild to moderate essential hypertension.
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  • 50
    ISSN: 1432-1041
    Keywords: ANP ; verapamil ; hypertension ; age
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a double-blind, placebo-controlled crossover study, the plasma atrial natriuretic peptide (ANP) levels of nine young and ten elderly hypertensive patients were compared after placebo and after treatment with 120 mg verapamil given three times daily over 4 weeks. During placebo, plasma ANP levels proved to be higher in elderly patients than in young subjects. Chronic treatment with verapamil induced a rise in ANP levels in both young and elderly patients with hypertension.
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  • 51
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    European journal of clinical pharmacology 39 (1990), S. 113-115 
    ISSN: 1432-1041
    Keywords: Furosemide ; 6-keto-PGF1α ; hypertension ; angiotensin II ; captopril ; urinary PGs ; PGI2
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of angiotensin II (AII) in Prostaglandin I2 (PGI2) production following furosemide has been examined in a placebo-controlled, cross-over study. Furosemide 20 mg was injected intravenously in eight hypertensive subjects already treated with oral captopril 25 mg or a matching placebo. Urinary excretion of 6-keto-PGF1α (a metabolite of PGI2) and PGE2, PRA and AII was increased following furosemide without captopril pretreatment. The rises in urinary 6-keto-PGF1α and PGE2, and plasma AII after furosemide were prevented by the captopril pretreatment. Urinary volume, sodium and furosemide were not affected by captopril. The data indicate that the effect of furosemide on PGI2 production, as reflected by the urinary excretion of 6-keto-PGF1α, was mediated by an action of AII.
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  • 52
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    European journal of clinical pharmacology 38 (1990), S. 303-303 
    ISSN: 1432-1041
    Keywords: cadralazin ; lupus erythematosus ; hydralazine ; SLE-syndrome ; case report ; hypertension ; adverse reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disappearance of a drug induced SLE syndrome in a 43 year old man, was described. He replaced antihypertensive agent hydralazine by an other vasodilatating agent cadralazine.
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  • 53
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    European journal of clinical pharmacology 38 (1990), S. 305-307 
    ISSN: 1432-1041
    Keywords: dilevalol ; carteolol ; hypertension ; vasodilator properties ; β-blocker ; renal function
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of 6 weeks of treatment with dilevalol 100 mg once daily, or carteolol 10 mg once daily, on renal blood flow (RBF), glomerular filtration rate (GFR) and total renal vascular resistance (TRR) were studied in 10 patients with mild-to-moderate essential hypertension in a randomised cross-over experiment. Both drugs lowered the systolic and diastolic blood pressures to a similar extent without altering the heart rate. Carteolol non-significantly decreased RBF by 9.2% and GFR by 12.3% without altering. TRR, whereas dilevalol produced a significant reduction in TRR by 13.2% (p〈0.05), a non-significant decrease in RBF by 4.6% and no change in GFR. Neither drug changed plasma osmotic pressure, serum total protein concentration, electrolytes or plasma aldosterone concentration. Plasma renin activity tended to be lower in the dilevalol phase as compared to the carteolol phase. The results suggest that dilevalol may cause a greater decrease in TRR and less reduction in GFR when compared to carteolol in patients with mild-to-moderate essential hypertension. The difference in the renal effects might be due to the difference in the potency of vasodilatory properties of both drugs at the doses applied.
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  • 54
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    European journal of clinical pharmacology 38 (1990), S. S89 
    ISSN: 1432-1041
    Keywords: hypertension ; hemodynamics ; alpha-blokkers ; beta-blockers ; multiple-action agents ; labetalol ; dilevalol ; carvedilol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A 20-year follow-up study of central hemodynamics in essential hypertension at rest and during exercise in 61 men with uncomplicated essential hypertension has clerarly shown that hemodynamic disturbances depend on the age of the subjects and the severity of the hypertensive state and that a shift in the hemodynamic alterations take place overtime. During 10- and 20-year follow-up, central hemodynamics changed towards a low cardiac-index (CI) — high total peripheral-resistance index (TPRI) pattern. With increasing age there was a gradual reduction in CI as well as stroke index (SI). The arteriovenous oxygen difference increased, particularly during exercise. The 20-year treatment with conventional drugs (beta-blockers and/or diuretics) did not prevent a marked increase in TPRI and a marked reduction in CI and SI in subjects initially 40–49 years of age. In recent years, beta-blockers with vasodilating activity have been introduced in the treatment of hypertension (labetalol, prizidilol, dilevalol and carvedilol). The hemodynamic effects of these compounds clearly differ from the changes induced during acute and chronic conventional beta-blocking treatment. In contrast to usual beta-blockers, these drugs reduce TPRI acutely and the reductions they produce in heart rate (HR) and CI are considerably lower. Our long-term data on labetalol (n =15), prizidilol (n =15) and dilevalol (n =17) indicate a persistent reduction in TPRI and litte or no decrease in exercise CI. Long-term data on carvedilol are not yet available. Approximately 70% of patients with mild to moderately severe essential hypertension achieved normal blood pressure during chronic treatment on beta-blockers with vasodilating activity.
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  • 55
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    European journal of clinical pharmacology 38 (1990), S. S120 
    ISSN: 1432-1041
    Keywords: carvedilol ; cerebral blood flow ; CBF autoregulation ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We studied the effects of oral carvedilol (20 mg/day) on cerebral blood flow (CBF) and CBF autoregulation in ten previous stroke patients with hypertension. Measurement of CBF was done by the argon inhalation method. CBF autoregulation was also studied by the (A-V)O2 method after stepwise reduction in systemic blood pressure. After 1 week of carvedilol administration, the mean arterial blood pressure showed an 18% decrease, with no significant changes in CBF, CBF autoregulation, or other cerebral circulation parameters. From these findings, it can be said that carvedilol is a potent anti-hypertensive agent that does not affect cerebral circulation parameters.
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  • 56
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    European journal of clinical pharmacology 39 (1990), S. S41 
    ISSN: 1432-1041
    Keywords: Enalapril ; hypertension ; renal function ; verapamil
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal, metabolic and antihypertensive effects of enalapril (E) and slow-release verapamil (V) were compared in a 2-month double-blind crossover trial in 22 patients with newly discovered essential hypertension. The glomerular filtration rate and renal vascular resistance were unaltered; renal blood flow was slightly decreased by V Serum Ca2+ increased and Na+ excretion declined after V. Serum lipids, glucose, and erythrocyte electrolytes were unchanged. Blood pressure (BP) was lower with E after half the maximum dosage compared with V but similar BP reductions were obtained after 2 months with the maximum dosage.
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  • 57
    ISSN: 1432-1041
    Keywords: doxazosin ; atenolol ; hypertension ; blood pressure ; essential ; serum lipids
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    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Doxazosin (mean dose 11 mg) given once daily in combination with 100 mg atenolol (n=44) was compared with placebo and atenolol (n=43) in a double-blind, multicenter study in patients with mild to moderate essential hypertension. In the atenolol/doxazosin-treated group, standing blood pressure significantly decreased by 17.0/12.3 mm Hg compared to 6.2/6.7 mm Hg in the atenolol/placebo group whereas supine blood pressure decreased by 13.2/9.8 mm Hg and 9.2/6.0 mm Hg, respectively in the two groups. Serum lipids did not change significantly in either group. The majority of side-effects reported were mild and transient. This study confirms that doxazosin may be safely combined with a beta-blocker. Doxazosin proved to be well tolerated and effective in patients with blood pressure refractory to atenolol alone.
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  • 58
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    European journal of clinical pharmacology 40 (1991), S. 453-460 
    ISSN: 1432-1041
    Keywords: Diltiazem ; metoprolol ; quality of life ; hypertension ; multicentre study ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary General well-being, adverse effects and antihypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were randomized to receive oral diltiazem 120–240–360 mg/day or metoprolol 50–100–200 mg/day. Each dose was given for a 4-week period as a forced titration regime. In all 119 patients, 59 and 60, respectively, on diltiazem and metoprolol completed the study protocol. There were dose-dependent reductions in supine and standing blood pressures (BP) after both diltiazem and metoprolol therapy. In the diltiazem group, supine BP was reduced by 10 (11)/10 (6) mm Hg (SBP/DBP) at the highest dose level, and the corresponding values for the metoprolol group were 7 (16)/8 (9) mm Hg (SBP/DBP). Target pressures (DBP ≤ 90 mm Hg and/or a reduction in DBP of ≥ 10%) were reached in 63% and 48% of the patients, respectively. The incidence and severity of dose-dependent adverse effects, as evaluated by spontaneous reports or open and direct questioning, did not differ between treatments. Subjective well-being, evaluated by a self-administered questionnaire, the MSE-profile, did not differ significantly between diltiazem and metoprolol therapy. However, after an initial slight deterioration, contentment and vitality tended to improve with increasing doses of diltiazem, while a dose-related deterioration in these variables was observed on metoprolol therapy. At the highest dose levels, contentment and vitality tended to be better in the diltiazem than the metoprolol group. Thus, diltiazem and metoprolol in daily doses of 120–360 mg and 50–200 mg, respectively, produce comparable and parallel reductions in supine and standing BP. However, while subjective well-being tended to improve with increasing doses of diltiazem, there was a negative trend for metoprolol. It is concluded that diltiazem, given as monotherapy to hypertensive patients, does not impair subjective well-being.
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  • 59
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    Molecular and cellular biochemistry 104 (1991), S. 45-50 
    ISSN: 1573-4919
    Keywords: hypertension ; Dahl rats ; angiotensin converting enzyme ; cardiac hypertrophy ; angiotensin II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Angiotensin II has previously been reported to have in vivo and in vitro cardiac hypertrophic effects. We used the salt-sensitive Dahl rat genetic strain to separate mechanical (pressure overload) vs. hormonal (renin-angiotensin system) input in cardiac hypertrophy. Blood pressure was significantly increased and left ventricular hypertrophy, as indexed by LV/BW ratios, was present at 7 and 15 days in rats receiving 4% and 8% NaCl compared to the 1% controls. There was no effect of the angiotensin converting enzyme inhibitor, enalapril maleate, on lowering the blood pressure in 8% NaCl-treated animals, however, there was a significant reduction in LV/BW ratio in 8% NaCl-treated animals that received this drug. Left ventricular angiotensinogen mRNA activity was significantly reduced in rats receiving 4% and 8% NaCl. In this model of hypertension the cardiac hypertrophy which develops is largely dependent on mechanical forces though there remains a significant contribution to this process from either circulating or localized angiotensin II production. Regulation of angiotensinogen gene expression in the hypertrophied left ventricle suggests that volume and electrolyte control of angiotensinogen gene expression in the heart and/or hereditary factors are predominant in the control of regulation of this gene in the left ventricle of Dahl rats.
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    Molecular and cellular biochemistry 96 (1990), S. 1-14 
    ISSN: 1573-4919
    Keywords: type I and III collagen ; fibrosis ; hypertension ; collagen gene expression ; collagen degradation
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    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The extracellular matrix of the myocardium contains an elaborate structural matrix composed mainly of fibrillar types I and III collagen. This matrix is responsible for the support and alignment of myocytes and capillaries. Because of its alignment, location, configuration and tensile strength, relative to cardiac myocytes, the collagen matrix represents a major determinant of myocardial stiffness. Cardiac fibroblasts, not myocytes, contain the mRNA for these fibrillar collagens. In the hypertrophic remodeling of the myocardium that accompanies arterial hypertension, a progressive structural and biochemical remodeling of the matrix follows enhanced collagen gene expression. The resultant significant accumulation of collagen in the interstitium and around intramyocardial coronary arteries, or interstitial and perivascular fibrosis, represents a pathologic remodeling of the myocardium that compromises this normally efficient pump. This report reviews the structural nature, biosynthesis and degradation of collagen in the normal and hypertrophied myocardium. It suggests that interstitial heart disease, or the disproportionate growth of the extracellular matrix relative to myocyte hypertrophy, is an entity that merits greater understanding, particularly the factors regulating types I and III collagen gene expression and their degradation.
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  • 61
    ISSN: 1573-8221
    Keywords: mesenteric microcriculation ; cardiac output ; Cardiogreen dilution method ; celiac ganglion ; hypertension
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  • 62
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    Bulletin of experimental biology and medicine 91 (1981), S. 18-21 
    ISSN: 1573-8221
    Keywords: arterial pressure ; hypertension ; capillary circulation
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  • 63
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    Bulletin of experimental biology and medicine 111 (1991), S. 598-602 
    ISSN: 1573-8221
    Keywords: electric field of the heart ; portal vein ; smooth muscle cells ; hypertension ; spontaneously hypertensive rats
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    Topics: Biology , Medicine
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