Determinants of angiotensin II generation during converting enzyme inhibition

Détails

ID Serval
serval:BIB_57988A34DB86
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Determinants of angiotensin II generation during converting enzyme inhibition
Périodique
Hypertension
Auteur(s)
Juillerat  L., Nussberger  J., Menard  J., Mooser  V., Christen  Y., Waeber  B., Graf  P., Brunner  H. R.
ISSN
0194-911X (Print)
Statut éditorial
Publié
Date de publication
11/1990
Volume
16
Numéro
5
Pages
564-72
Notes
Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't --- Old month value: Nov
Résumé
The reaction of the renin-angiotensin system to acute angiotensin converting enzyme inhibition was investigated in a single-blind, crossover study in nine normal volunteers receiving two out of three regimens in random order: the new converting enzyme inhibitor benazepril (20 mg once or 5 mg four times at 6-hour intervals) or enalapril (20 mg). Plasma converting enzyme activity, drug levels, angiotensin I and angiotensin II, active renin, and aldosterone were measured before and 1-4 hours and 14-30 hours after drug intake. Baseline in vitro plasma converting enzyme activity was 97 +/- 15 nmol/ml/min (mean +/- SD) when Hip-Gly-Gly was used as substrate, but with carbobenzoxy-Phe-His-Leu (Z-Phe-His-Leu) or angiotensin I as substrate it was only 20 +/- 4 and 1.7 +/- 0.3 nmol/ml/min, respectively. Discriminating power at peak converting enzyme inhibition was enhanced with the two latter substrates. In vivo converting enzyme activity was estimated by the plasma angiotensin II/angiotensin I ratio, which correlated well with in vitro converting enzyme activity using Z-Phe-His-Leu as substrate (r = 0.76, n = 252). Angiotensin II levels returned to baseline less than 24 hours after drug administration, whereas in vitro and in vivo converting enzyme activity remained considerably inhibited and active renin together with angiotensin I levels were still elevated. A close linear relation was found between plasma angiotensin II and the angiotensin I/drug level ratio (r = 0.91 for benazeprilat and r = 0.88 for enalaprilat, p less than 0.001). Thus, plasma angiotensin II truly reflects the resetting of the renin-angiotensin system at any degree of converting enzyme inhibition. The ratio of plasma angiotensin II to angiotensin I represents converting enzyme inhibition more accurately than in vitro assays, which vary considerably depending on substrates and assay conditions used.
Mots-clé
Angiotensin I/blood Angiotensin II/*biosynthesis/blood Angiotensin-Converting Enzyme Inhibitors/blood/*pharmacology Humans Male Peptidyl-Dipeptidase A/blood Renin/blood
Pubmed
Web of science
Création de la notice
05/03/2008 17:39
Dernière modification de la notice
20/08/2019 15:11
Données d'usage