Biochemical effects of prolonged renin inhibition in marmosets.
The renin inhibitor CGP 29,287 was administered continuously for 7 days (30 mg/kg per day, intraperitoneally, via osmotic minipumps) to normotensive marmosets fed a low-salt diet. As a control, another group of marmosets was given vehicle only. After 7 days of treatment, the mean arterial blood pressure of the CGP 29,287-treated marmosets was significantly lowered by about 23 mmHg. Plasma immunoreactive total and active renin were increased 10- and sevenfold, respectively, whereas plasma renin activity (PRA) was reduced by 95%. Plasma angiotensin II (Ang II) and aldosterone were also reduced (by 97 and 85%, respectively). Serum angiotensin converting enzyme activity was unchanged and there were no differences in plasma concentrations of electrolytes, urea or creatinine between CGP 29,287-treated and control marmosets. These results indicate that although renin release is markedly stimulated after continuous administration of a renin inhibitor for 7 days, the formation of Ang II and aldosterone, the active hormones of the renin-angiotensin system, is substantially reduced.
Wood
J M
JM
Cardiovascular Research Department, Ciba-Geigy Limited, Basel, Switzerland.
Jobber
R A
RA
Baum
H P
HP
de Gasparo
M
M
Nussberger
J
J
D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002144:Callithrix; D006339:Heart Rate / Q000187:drug effects; D007260:Infusion Pumps; D009842:Oligopeptides; D012083:Renin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000092502:Renin Inhibitors
D000450:Aldosterone; D000804:Angiotensin II; D009842:Oligopeptides; D012083:Renin; D000092502:Renin Inhibitors; C045501:CGP 29287