Effects of SCH 34826, an orally active inhibitor of atrial natriuretic peptide degradation, in healthy volunteers.

Détails

ID Serval
serval:BIB_B2F2B38AFEF9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effects of SCH 34826, an orally active inhibitor of atrial natriuretic peptide degradation, in healthy volunteers.
Périodique
Clinical pharmacology and therapeutics
Auteur(s)
Burnier M., Ganslmayer M., Perret F., Porchet M., Kosoglou T., Gould A., Nussberger J., Waeber B., Brunner H.R.
ISSN
0009-9236
Statut éditorial
Publié
Date de publication
1991
Peer-reviewed
Oui
Volume
50
Numéro
2
Pages
181-91
Langue
anglais
Notes
Publication types: Clinical Trial ; Controlled Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
Atrial natriuretic peptide is cleared from plasma by clearance receptors and by enzymatic degradation by way of a neutral metalloendopeptidase. Inhibition of neutral metalloendopeptidase activity appears to provide an interesting approach to interfere with metabolism of atrial natriuretic peptide to enhance the renal and haemodynamic effects of endogenous atrial natriuretic peptide. In this study, the effects of SCH 34826, a new orally active neutral metalloendopeptidase inhibitor, have been evaluated in a single-blind, placebo-controlled study involving eight healthy volunteers who had maintained a high sodium intake for 5 days. SCH 34826 had no effect on blood pressure or heart rate in these normotensive subjects. SCH 34826 promoted significant increases in excretion of urinary sodium, phosphate, and calcium. The cumulative 5-hour urinary sodium excretion was 15.7 +/- 7.3 mmol for the placebo and 22.9 +/- 5, 26.7 +/- 6 (p less than 0.05), and 30.9 +/- 6.8 mmol (p less than 0.01) for the 400, 800, and 1600 mg SCH 34826 doses, respectively. During the same time interval, the cumulative urinary phosphate excretion increased by 0.3 +/- 0.4 mmol after placebo and by 1.5 +/- 0.3 (p less than 0.01), 1.95 +/- 0.3 (p less than 0.01), and 2.4 +/- 0.4 mmol (p less than 0.001) after 400, 800, and 1600 mg SCH 34826, respectively. There was no change in diuresis or excretion of urinary potassium and uric acid. The natriuretic response to SCH 34826 occurred in the absence of any change in plasma atrial natriuretic peptide levels but was associated with a dose-dependent elevation of urinary atrial natriuretic peptide and cyclic guanosine monophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
Mots-clé
Analysis of Variance, Atrial Natriuretic Factor, Blood Pressure, Dioxolanes, Dipeptides, Dose-Response Relationship, Drug, Heart Rate, Hemodynamics, Humans, Male, Natriuresis, Reference Values, Renal Circulation, Sodium, Dietary
Pubmed
Web of science
Création de la notice
05/03/2008 16:40
Dernière modification de la notice
20/08/2019 15:21
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