Comparison of Chronic Inhibition of Renin and Converting Enzyme in the Marmoset

Abstract

The primate-specific renin inhibitor CGP 29287 (30 mg/kg/d, n = 5) or the converting-enzyme inhibitor CGS 14831 (30 mg/kg/d, n = 8) were administered by continuous intraperitoneal infusion via osmotic minipumps to normotensive marmosets fed a low salt diet. CGP 29287 and CGS 14831 induced a similar reduction in blood pressure after 2 days of administration (-22 +/- 6, SEM and -24 +/- 6 mmHg respectively). The hypotensive response persisted at 7 days (-20 +/- 3 and -22 +/- 8 mmHg respectively). Despite the fall in blood pressure, heart rate was not changed after either inhibitor. Blood pressure and heart rate remained stable in control marmosets that received vehicle only (0.9% saline). Plasma renin activity was inhibited after CGP 29287 (100% at day 2 and 75% at day 7) and increased after CGS 14831 (4 and 3 fold on days 2 and 7 respectively). Total plasma immunoreactive renin was increased to a similar extent after both inhibitors (approximately 5 fold on days 2 and 7). These findings show that a similar hypotensive response is induced in sodium-depleted primates after chronic inhibition of renin or converting enzyme. Thus the fall in blood pressure after chronic treatment with either inhibitor appears to be mainly due to the blockade of the renin-angiotensin system and the consequent reduction in endogenous angiotensin II formation.