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

Details

Serval ID
serval:BIB_B2F2B38AFEF9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effects of SCH 34826, an orally active inhibitor of atrial natriuretic peptide degradation, in healthy volunteers.
Journal
Clinical pharmacology and therapeutics
Author(s)
Burnier M., Ganslmayer M., Perret F., Porchet M., Kosoglou T., Gould A., Nussberger J., Waeber B., Brunner H.R.
ISSN
0009-9236
Publication state
Published
Issued date
1991
Peer-reviewed
Oui
Volume
50
Number
2
Pages
181-91
Language
english
Notes
Publication types: Clinical Trial ; Controlled Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
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)
Keywords
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
Create date
05/03/2008 16:40
Last modification date
20/08/2019 15:21
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