cgp-29287 and benazeprilat

To assess the effects of inhibition of the renin-angiotensin system at different levels on plasma concentrations of components of the system and on renin and angiotensinogen gene expression, marmosets on a low-sodium diet were treated for 1 wk by continuous intraperitoneal infusion with either the renin inhibitor CGP-29287, the ACE inhibitor benazeprilat, the angiotensin II antagonist valsartan, the renin inhibitory monoclonal antibody R-3-36-16, or vehicle. Plasma total immunoreactive renin increased (14- to 20-fold) after all three modes of interference. Plasma angiotensinogen was significantly reduced in the benazeprilat- and valsartan-treated marmosets but not in the CGP-29287-treated animals. Plasma concentration of angiotensin II was significantly decreased in the benazeprilat-, CGP-29287-, and R-3-36-16-treated marmosets and was increased in the valsartan-treated marmosets. Kidney renin mRNA level increased 8- to 15-fold in all groups. Hepatic angiotensinogen mRNA level increased with CGP-29287 treatment but decreased with the other treatments. Kidney angiotensinogen mRNA level was not affected by any treatment. Different modes of inhibition of the renin-angiotensin system have different effects on plasma components of the system and liver angiotensinogen expression.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Antibodies, Monoclonal; Benzazepines; Blood Pressure; Callithrix; Female; Kidney; Liver; Male; Oligopeptides; Renin; Renin-Angiotensin System; RNA, Messenger; Tetrazoles; Time Factors; Valine; Valsartan

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.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Callitrichinae; Female; Heart Rate; Male; Oligopeptides; Peptidyl-Dipeptidase A; Renin