Hypertension, Vol 16, 564-572, Copyright © 1990 by American Heart Association
L Juillerat, J Nussberger, J Menard, V Mooser, Y Christen, B Waeber, P Graf and HR Brunner
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.
ARTICLES
Determinants of angiotensin II generation during converting enzyme inhibition
Hypertension Division, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
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|
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