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  • 1
    ISSN: 1432-1041
    Keywords: Benserazide ; decarboxylase inhibition ; alpha-methyldopa ; essential hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a single-blind study, the dopa-decarboxylase inhibitor benserazide (375 mg/day for 3 days and 750 mg/day for further 3 days) and a placebo were given orally in combination with individually effective doses of alpha-methyldopa (mean 1.5 g/day) to 3 hospitalized patients with essential hypertension. Alpha-methyldopa (α-MD) alone lowered blood pressure from 165/107 to 136/93 mm Hg (P〈0.05). Benserazide did not alter the hypotensive effect of α-MD, although the decarboxylation of α-MD was markedly reduced, as shown by the urinary excretion of alpha-methyldopamine (α-MDA). During administration of α-MD alone, the ratio α-MD/α-MDA in urine of the 3 patients was 8:1, 7:1 and 22:1, respectively. When benserazide 375 mg/day was added the ratio rose to 31:1, 31:1 and 35:1; the ratio was 37:1, 18:1 and 46:1 at the higher dose of inhibitor. In a double-blind crossover study the effect on blood pressure of 3 weeks of treatment with α-MD (mean 1.75 mg/day), benserazide (375 mg/day), placebo and their combinations were compared in 5 hypertensive subjects. Again, benserazide did not influence the antihypertensive action of α-MD. To study whether benserazide entered the CNS, a single oral dose of14C-benserazide of 125 mg was given to 2 patients who were to undergo diagnostic lumbar puncture. Two hours after intake of the labelled drug, when radioactivity in blood had reached a maximum, the concentration of radioactivity in spinal fluid was less than 1% of the plasma level. Thus, the antihypertensive action of α-MD was not influenced by oral doses of the decarboxylase inhibitor benserazide. The results suggest that benserazide in doses up to 750 mg/day does not affect central decarboxylation of α-MD and that this antihypertensive agent lowers blood pressure by a central action.
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  • 2
    ISSN: 1432-1041
    Keywords: Dopamine-β-hydroxylase ; dopamine infusion ; blood pressure ; plasma ; man ; inter-individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to study the function of dopamine-β-hydroxylase (DBH) in human plasma, dopamine, its natural substrate, was infused intravenously in 22 healthy volunteers. Their plasma DBH activities showed great interindividual variations (31–301 units/ml). The infusion rates of dopamine required to increase systolic blood pressure (BP) by 30 mm Hg differed considerably between the subjects, and ranged from 3,0 to 11,6 µg/kg/min. No correlation could be shown between the various dopamine doses and individual plasma levels of DBH. It was concluded, therefore, that plasma DBH in the blood stream was enzymatically inactive. Experiments with human plasma DBH in vitro also support this interpretation. Consequently, interindividual differences in the effects on BP during dopamine infusion cannot be due to pressor effects of noradrenaline synthesized by plasma DBH.
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  • 3
    ISSN: 1432-1041
    Keywords: propranolol ; noradrenaline ; normotension ; withdrawal ; exercise ; effect duration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of acute and chronic treatment with the adrenergic beta-receptor blocking agent propranolol (P) on blood pressure (BP), heart rate (HR) and plasma catecholamine concentration (CA) was studied in 7 normotensive healthy volunteers, and in 5 normotensive patients with cardiac neurosis, at rest, during physical exercise and after sudden withdrawal of the drug. The first oral dose of P 120 mg as well as chronic treatment (3×80 mg/day for 3 months) caused a significant reduction in HR and supine BP. Resting values of CA were not changed. After sudden withdrawal of the long-term therapy with P, supine BP and HR returned to normal, and again, resting levels of CA remained unchanged. A physical exercise test, performed 2 1/2 days after withdrawal of the betablocker, was not indicative of a transient sympathetic hyper-response. Striking effects of the drug on CA were observed during acute and chronic treatment with P when physical exercise was performed (bicycle ergometer, 150 W). Exercise values of CA were about twice as high during P treatment as without the drug, when the exercise test was performed 2 h after the first oral dose. At the same time, however, exercise BP and HR were significantly reduced. Similar reactions during the exercise test were also seen during chronic treatment with P, when the test was performed 2 hours after the last dose of the drug. But, when the exercise test was undertaken during chronic treatment 8 h after drug intake, the drug effect on CA had disappeared, whereas the effects on BP and HR still were present. The dissociation during chronic treatment between the effect on the duration of plasma CA and that of the pharmacodynamic responses to beta-adrenergic blockade with P is the principal finding of the study. A hypothesis is offered for interpretation of the observations. The time interval between measurement of drug effect and drug intake must be carefully observed in assessing different or controversial drug responses.
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  • 4
    ISSN: 1432-1440
    Keywords: Adrenaline ; Noradrenaline ; Adrenal medulla ; Pheochromocytoma ; Hypertension ; Adrenalin ; Noradrenalin ; Nebennierenmark ; Phäochromozytom ; Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 10 Personen (5 mit normalem Blutdruck, 4 mit essentieller Hypertonie, 1 mit renaler Hypertonie) wurden die lokalen Katecholaminkon-zentrationen im Blut der Vena suprarenalis, Vena renalis, Vena cava inferior und Vena iliaca mit einer radioenzymatischen Methode bestimmt. Es fanden sich folgende Konzentrationen pro Milliliter Plasma: (1) In der Vena suprarenalis der linken Nebenniere 13,87±8,18 ng Adrenalin und 2,82±1,82 ng Noradrenalin; (2) in der Vena renalis, nach der Mischung mit dem Blut der einströmenden Vena suprarenalis, 1,44±1,13 ng Adrenalin und 0,37±0,18 ng Noradrenalin; (3) in der Vena cava inferior, cranial der Nierenvenenzuflüsse, 0,16±0,10 ng Adrenalin und 0,30±0,10 ng Noradrenalin; (4) in der Kreislaufperipherie, zum Beispiel im Blut der Vena iliaca, betrug die Adrenalinkonzentration mit 0,09±0,03 ng nur noch 1/154 der ursprünglichen Konzentration im Nebennierenvenenblut, die Noradrenalinkonzentration lag hier bei 0,24±0,14 ng/ml Plasma. Unter der Annahme, daß das vom Nebennierenmark freigesetzte Noradrenalin den gleichen Verteilungs- und Eliminationsmechanismen wie Adrenalin unterliegt, wurde errechnet, daß unter basalen Sekretionsbedingungen im Durchschnitt nur 7,5% des in der Kreislaufperipherie zirkulierenden Noradrenalins aus dem Nebennierenmark stammen. Die Adrenalin- und Noradrenalinkonzentration im Nebennierenvenenblut bei Patienten mit essentieller Hypertonie war nicht höher als bei Personen mit normalem Blutdruck.
    Notes: Summary In 10 human subjects (5 with normal blood pressure, 4 with essential hypertension, 1 with renal hypertension) local catecholamine levels in blood of suprarenal vein, renal vein, inferior vena cava and iliac vein were determined by a radioenzymatical method. The following concentrations per ml plasma were found: (1) in the suprarenal vein of the left adrenal gland 13.87±8.18 ng adrenaline and 2.82±1.82 ng noradrenaline; (2) in the left renal vein, after confluence of suprarenal with renal blood, 1.44±1.13 ng adrenaline and 0.37±0.18 ng noradrenaline; (3) in the inferior vena cava, cranial of both renal veins, 0.16±0.10 ng adrenaline and 0.30±0.10 ng noradrenaline; (4) in periphery, as in the iliac vein, the plasma adrenaline concentration was only 0.09±0.03 ng/ml, corresponding to 1/154 of suprarenal vein blood concentration; the noradrenaline concentration in iliac vein was 0.24±0.14 ng/ml plasma. Assuming that noradrenaline released from the adrenal medulla follows the same distribution and elimination mechanisms as adrenaline, it was calculated that only 7.5% of noradrenaline found under basal conditions in the periphery of the circulation, originates from the adrenal medulla. The adrenaline and noradrenaline concentration in blood of suprarenal vein of patients with essential hypertension was not higher than the concentrations found in subjects with normal blood pressure.
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  • 5
    ISSN: 1432-1440
    Keywords: Plasmakatecholamine ; Dopamin-β-Hydroxylase ; Essentielle Hypertonie ; Körperliche Belastung ; Plasma catecholamines ; Dopamine-β-hydroxylase ; Essential hypertension ; Physical exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In 8 normotensive subjects and in 8 patients with essential hypertension total catecholamine content and dopamine-β-hydroxylase (DBH) activity in plasma were measured at rest and during physical exercise. Catecholamine levels at rest were significantly higher in the hypertensive than in the normotensive persons whereas the 2 groups of subjects did not differ in DBH activity at rest. At a work load of 150 watts there was a more pronounced increase of the catecholamine concentrations and of the DBH activity in the hypertensive patients than in the normotensives. One may conclude from the data that there is an increased sympathetic nerve activity in patients with essential hypertension.
    Notes: Zusammenfassung Bei 8 Normotonikern sowie bei 8 Patienten mit essentieller Hypertonie wurden die Konzentrationen der Gesamtkatecholamine und die Aktivität der Dopamin-β-Hydroxylase (DBH) im Plasma unter Ruhebedingungen und während körperlicher Belastung gemessen. Bei den Hypertonikern waren die Ruhewerte der Katecholamine signifikant höher als bei den Normotonikern, während die DBH-Aktivität unter diesen Bedingungen bei beiden Gruppen gleich war. Bei einer Ergometerbelastung von 150 Watt stiegen die Katecholaminspiegel und die DHB-Aktivität bei den Hochdruckkranken stärker an als bei den Probanden mit normalem Blutdruck. Aus den Untersuchungsergebnissen kann man schließen, daß bei Patienten mit essentieller Hypertonie eine erhöhte Aktivität sympathischer Nerven besteht.
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