Hemodynamic and biochemical consequences of renin inhibition by infusion of CGP 38560A in normal volunteers.
Hemodynamic and biochemical effects of the new renin inhibitor CGP 38560A (molecular weight 826) were tested in 15 healthy volunteers after a single-blind, randomized, placebo-controlled protocol. At a 2-week interval, groups of five subjects received a 30-minute infusion of either 5% dextrose or CGP 38560A 50, 125, or 250 micrograms/kg. Blood pressure, heart rate, plasma renin activity, active and total renin, angiotensin-(1-8)octapeptide (angiotensin II), and aldosterone were sequentially measured up to 3 hours from the onset of the infusion. There was no consistent change in blood pressure or heart rate. Plasma renin activity and angiotensin II decreased dose dependently, and peak suppression was observed at the end of the infusion of CGP 38560A and after the 250-micrograms/kg dose. Plasma renin activity fell from 1.0 +/- 0.19 (mean +/- SEM) to less than 0.05 ng/ml/hr in all five subjects (p less than 0.001), and angiotensin II fell from 7.7 +/- 1.2 to 2.6 +/- 0.9 femtomole/ml (p less than 0.01). Active renin rose fourfold from 24 +/- 1.9 to 98 +/- 14 pg/ml (p less than 0.001) at the end of the infusion of the high dose. Plasma angiotensin II returned toward its initial values much faster than plasma renin activity and active renin. In conclusion, CGP 38560A was well tolerated. It induced a dose-dependent decrease in angiotensin II and plasma renin activity and a long-lasting and dose-dependent rise in active renin. The doses used did not reduce plasma angiotensin II maximally despite reduction of plasma renin activity to unmeasurable levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Nussberger
J
J
Hypertension Division, University Hospital, Lausanne, Switzerland.
Delabays
A
A
De Gasparo
M
M
Cumin
F
F
Waeber
B
B
Brunner
H R
HR
Ménard
J
J
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D012016:Reference Values; D012083:Renin / Q000097:blood; D000092502:Renin Inhibitors
D000450:Aldosterone; D000804:Angiotensin II; D009842:Oligopeptides; D012083:Renin; D000092502:Renin Inhibitors; C060150:CGP 38560