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  • 1
    Electronic Resource
    Electronic Resource
    The chloride concentration in the lateral intercellular spaces of MDCK cell monolayers (1995)
    Springer
    The journal of membrane biology 144 (1995), S. 21-30 
    Details
    ISSN: 1432-1424
    Keywords: Epithelia ; Fluid transport ; Cl transport ; ABQ ; Fluorescence microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract We measured the Cl concentration of the lateral intercellular spaces (LIS) of MDCK cell monolayers, grown on glass coverslips, by video fluorescence microscopy. Monolayers were perfused at 37°C either with HEPES-buffered solutions containing 137 mm Cl or bicarbonate/CO2-buffered solutions containing 127 mm Cl. A mixture of two fluorescent dyes conjugated to dextrans (MW 10,000) was microinjected into domes and allowed to diffuse into the nearby LIS. The Cl sensitive dye, ABQ-dextran, was selected because of its responsiveness at high Cl concentrations; a Clinsensitive dye, Cl-NERF-dextran, was used as a reference. Both dyes were excited at 325 nm, and ratios of the fluorescence intensity at spectrally distinct emission wavelengths were obtained from two intensified CCD cameras, one for ABQ-dextran the other for Cl-NERFdextran. LIS Cl concentration was calibrated in situ by treating the monolayer with digitonin or ouabain and varying the perfusate Cl between 0 and 137 mm (HEPES buffer) or between 0 and 127 mm (bicarbonate/CO2 buffer). LIS Cl in HEPES-buffered solutions averaged 176 ± 19 mm (n = 12), calibrated with digitonin, and 170 ± 9 mm (n = 12), calibrated with ouabain. LIS Cl in bicarbonate/CO2-buffered solutions averaged 174 ± 10 mm (n = 7) using the ouabain calibration. The Cl concentration of MDCK cell domes, measured with Clsensitive microelectrodes and by microspectrofluorimetry, did not differ significantly. Images of the LIS at 3 focal planes, near the tight junction, midway and basal, failed to reveal any gradients in Cl concentration along the LIS. LIS Cl changed rapidly in response to perfusate Cl with characteristic times of 0.8 ± 0.1 min (n = 21) for Cl decrease and 0.3 ± 0.04 min (n=21) for Cl increase. In conclusion, (i) Cl concentration is higher in the LIS than in the bathing medium, (ii) no gradients of Cl along the depth of LIS are detectable, (iii) junctional Cl permeability is high.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238413
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ketanserin in patients with essential hypertension (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 259-265 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; ketanserin-ol ; pharmacokinetics ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of ketanserin and its main metabolite ketanserin-ol, and the antihypertensive effects of intravenous, single oral and chronic oral (40 mg once daily) administration of ketanserin, have been investigated in a single blind study of 10 patients with uncomplicated mild hypertension. Ketanserin had a terminal half-life of 29.2 h, a plasma clearance of 518 ml/min and a volume of distribution of 18.0 l/kg. Chronic oral intake of 40 mg ketanserin (tablet formulation) gave a peak concentration of unchanged ketanserin of 88 ng/ml after 1.1 h. Its absolute bioavailability was 48%. During chronic therapy the maximal concentration of ketanserin-ol was 208 ng/ml and its half-life of elimination was 35.0 h. As this metabolite can be oxidized back to ketanserin, it contributes to the prolonged half-life of unchanged ketanserin seen during chronic therapy. The blood pressure was reduced by approximately 15% by oral ketanserin. The maximal reduction in blood pressure coincided with the peak concentration of unchanged ketanserin. During chronic therapy with 40 mg once daily blood pressure was reduced over 24 h. The heart rate was slightly reduced and the cardiovascular responses and the plasma noradrenaline concentrations during isometric exercise were only slightly influenced by ketanserin therapy. Thus, unchanged ketanserin has a relatively long half-life during chronic oral therapy and its pharmacokinetics in middle-aged hypertensive patients is similar to that in normal young volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607573
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  • 3
    Electronic Resource
    Electronic Resource
    Flow resistance and its components in hypertensive men treated with the calcium antagonist isradipine (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 463-468 
    Details
    ISSN: 1432-1041
    Keywords: Hypertension, Isradipine ; haemorheology, haemodynamics, calcium antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The components of blood flow resistance were investigated in 14 men with essential hypertension (diastolic blood pressure higher or equal to 100 mmHg) before and after treatment with the dihydropyridine calcium antagonist-isradipine. Isradipine reduced intraarterial blood pressure by decreasing the total (placebo 5.1 U · mPa−1·s−1; isradipine 3.9 U·mPa−1·s−1), and renal (placebo 48.9 U·mPa−1· s−1, isradipine 35.4 U·mPa−1·s−1) vascular hindrance, the blood viscosity being unchanged. Arterial compliance was increased by isradipine (placebo 1.03 ml·mm Hg−1; isradipine 1,25 ml·mm Hg−1). The pressor response to adrenergic alpha stimulation with phenylephrine was decreased during treatment with the calcium antagonist. The compliance of the venous system was not changed by the treatment with isradipine. Haemorheological parameters were stable throughout the study but some changes in the correlations between the different rheological parameters were observed. The present study indicates that the antihypertensive effect of the dihydropyridine calcium antagonist isradipine was the result of functional modulation of the small and large arteries, the venous system and the flow properties of blood being unaffected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02285086
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  • 4
    Electronic Resource
    Electronic Resource
    Metabolic effects of oral salbutamol in late pregnancy (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 95-99 
    Details
    ISSN: 1432-1041
    Keywords: Salbutamol ; metabolic effects ; cyclic AMP ; β-adrenergic agonist ; pregnancy ; carbohydrate metabolism ; lipid metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ten women in late pregnancy were given an oral dose of salbutamol 4 mg. Heart-rate and blood-pressure were recorded and blood-samples for measurement of cyclic AMP, C-peptide, glucose, lactate, glycerol, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (3-HB) were collected every 30 min for 120 min. In seven of the women the same experiment was performed without the salbutamol. After salbutamol maternal heart-rate was significantly increased at 30 and 90 min, and diastolic blood-pressure was significantly decreased between 30 and 120 min; systolic blood-pressure was unaltered. Plasma cyclic AMP was significantly increased by salbutamol at 30 and 120 min and C-peptide at 60 min. Plasma glucose was significantly elevated 60 min after salbutamol and glycerol after 90 min. Plasma NEFA and 3-HB increased both with and without the drug, with a tendency towards higher levels in the group that received salbutamol. Lactate levels were unchanged after salbutamol and fell when the drug was not given, but the difference was not significant. The results show clear circulatory and metabolic effects of a single clinical dose of salbutamol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607438
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  • 5
    Electronic Resource
    Electronic Resource
    Acute systemic and renal haemodynamic effects and long-term antihypertensive action of cadralazine in patients pretreated with β-blockers and diuretics (1987)
    Springer
    European journal of clinical pharmacology 31 (1987), S. 513-518 
    Details
    ISSN: 1432-1041
    Keywords: cadralazine ; hypertension ; haemodynamic effects ; renal blood flow ; glomerular filtration ; renal function ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects of the hydralazine-related compound cadralazine (2-{3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl}ethyl carbazate, ISF 2469), were investigated in 16 patients with primary hypertension concurrently treated with β-blockers and diuretics. The protocol included a double-blind placebo controlled haemodynamic evaluation after the first tablet and two 4-week double-blind placebo controlled cross-over periods followed by an open evaluation during 2 months. Cadralazine induced a moderate, prolonged fall in blood pressure that was associated with vasodilatation and slight increases in cardiac output (dye-dilution) and heart rate. Renal plasma flow (PAH) and glomerular filtration rate (51Cr-EDTA) were not significantly influenced, but the filtration fraction was reduced. Plasma concentrations of noradrenaline and adrenaline rose, whereas plasma renin activity was unchanged. The haemodynamic parameters were not correlated with the plasma concentrations of cadralazine. During chronic cadralazine treatment the supine blood pressure was significantly lower than during the double-blind placebo phase (160/93 vs 174/102 mmHg). The compound was generally well tolerated but the body weight increased slightly (1.1 kg), probably because of fluid retention. Several patients who had previously experienced side effects with hydralazine, including one with hydralazine-syndrome, tolerated cadralazine well. This suggests that cadralazine does not cross-react with hydralazine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606622
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  • 6
    Electronic Resource
    Electronic Resource
    Serotonin-induced platelet aggregation predicts the antihypertensive response to serotonin receptor antagonists (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 121-125 
    Details
    ISSN: 1432-1041
    Keywords: Hypertension ; Ketanserin ; platelet aggregation ; serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The 5-HT2-receptor antagonist ketanserin (20–40 mg b.i.d.) was administered to 62 patients of both sexes with uncomplicated primary hypertension. After 4 weeks of treatment about 50% of the patients had reached the target diastolic blood pressure of 90 mm Hg or below. Interindividual variability was large. In a retrospective analysis the variability could not be explained by sex or the dose of ketanserin. There was a weak association between age and systolic blood pressure response (r=0,24; P=0.06), which could be entirely accounted for by the higher base line blood pressure in the elderly patients. In one group of patients (n=12), the ex vivo aggregation to serotonin (10−6 M) was studied during treatment with placebo and ketanserin. Ketanserin completely inhibited 5-HT-induced aggregation in all patients. There was a close correlation between the area under the 5-HT-induced platelet aggregation curve during placebo and the subsequent reduction in diastolic blood pressure after 4 weeks of treatment with ketanserin. The present data suggest that the blood pressure response to ketanserin can be predicted from the ex vivo sensitivity of platelets to serotonin. By implication, they also support a role for serotonergic mechanisms in hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315468
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  • 7
    Electronic Resource
    Electronic Resource
    Ketanserin in essential hypertension: Effects during rest and exercise (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 307-312 
    Details
    ISSN: 1432-1041
    Keywords: ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037939
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  • 8
    Electronic Resource
    Electronic Resource
    Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 651-656 
    Details
    ISSN: 1432-1041
    Keywords: Yohimbine ; pharmacokinetics, noradrenaline, adrenaline, neuropeptide Y, healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of yohimbine and its effects on sympathoadrenal function were studied in 13 young, healthy, male volunteers after an IV bolus dose of 0.25 or 0.5 mg · kg−1. Pharmacokinetic analysis showed that distribution was rapid, with a half life between 0.4 and IS min, and the elimination half life ranged between 0.25 and 2.5 h. The volume of distribution (Vss) was 741, (range 26 to 1271). Only 0.5 to 1 % of unchanged yohimbine was found in the urine, indicating that the major part of the drug was eliminated by hepatic clearance. Total plasma clearance was 1171. h−1, which exceeds the hepatic plasma flow. This means that yohimbine is a high extraction drug with considerable extra-hepatic metabolism. Fractional urine sampling revealed that 0.5-1 % of unchanged yohimbine was excreted in urine in a biphasic manner. The data also suggested the existence of a slower elimination phase, with a half life of 13 h. The venous plasma concentration of noradrenaline (NA) increased 3-fold within 15 min after the yohimbine injection while plasma adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY LI) remained unchanged. The plasma concentration-effect relationship of the changes in circulating NA followed counter-clockwise hysteresis. The results show that the hyperadrenergic state elicited by therapeutic doses of theα 2-adrenergic autoreceptor antagonist, yohimbine, is due to an interaction with NA but not to release of A or NPY in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02284967
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  • 9
    Electronic Resource
    Electronic Resource
    Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients (1996)
    Springer
    European journal of clinical pharmacology 50 (1996), S. 259-264 
    Details
    ISSN: 1432-1041
    Keywords: Key words Moexipril ; Hypertension ; Hydrochloro-thiazide; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To compare the antihypertensive efficacy of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, to treatment with hydrochlorothiazide (HCTZ). Patients: Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension. Methods: This was a multicentre, placebo-controlled, double-blind study with a parallel group design. Subjects with a sitting diastolic blood pressure (DBP) ≥ 95 mmHg were randomized to monotherapy with placebo, moexipril 7.5 mg o.d., moexipril 15 mg o.d. or HCTZ 25 mg o.d. for 8 weeks. Results: Throughout the study period treatment with moexipril and HCTZ resulted in significant reductions of DBP compared with placebo, but there were no significant differences between the active treatment groups. At end point the adjusted mean reductions were 10.5, 8.7 and 10.1 mmHg in the HCTZ, moexipril 7.5 mg and moexipril 15 mg groups, respectively, compared to 3.9 mmHg in the placebo group. Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels. Otherwise, both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group. Conclusion: Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050104
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  • 10
    Electronic Resource
    Electronic Resource
    Density matrix averaged atomic natural orbital (ANO) basis sets for correlated molecular wave functions (1991)
    Springer
    Theoretical chemistry accounts 79 (1991), S. 419-432 
    Details
    ISSN: 1432-2234
    Keywords: ANO ; Correlated molecular wave functions ; Second row atoms ; Ionization potential ; Electron affinity ; Polarizability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Generally contracted basis sets for second row atoms have been constructed using the Atomic Natural Orbital (ANO) approach, with modifications for allowing symmetry breaking and state averaging. The ANOs are constructed by averaging over several atomic states, positive and negative ions, and atoms in an external electric field. The contracted basis sets give virtually identical results as the corresponding uncontracted sets for the atomic properties, which they have been designed to reproduce. The design objective has been to describe the ionization potential, the electron affinity, and the polarizability as accurately as possible. The result is a set of well balanced basis sets for molecular calculations. The starting primitive sets are 17s12p5d4f for the second row atoms Na-Ar. Corresponding ANO basis sets for first row atoms have recently been published.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01112569
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