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.

Haemodynamic effects of acute and chronic renin inhibition in marmosets.

We have developed marmoset models for the in vivo evaluation of primate-specific inhibitors of human renin. After acute intravenous administration to normotensive sodium-depleted marmosets, renin inhibitors of different structural types induced a maximum hypotensive response of a magnitude similar to that induced after angiotensin converting enzyme (ACE) inhibition. The response was prevented by pretreatment with an ACE inhibitor.

Comparison of chronic inhibition of renin and converting enzyme in the marmoset.

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).

Sustained reduction in blood pressure during chronic administration of a renin inhibitor to normotensive marmosets.

In this study, the hypotensive efficacy of a renin inhibitor was investigated during chronic administration. The renin inhibitor CGP 29,287 was administered by continuous intraperitoneal infusion with osmotic mini-pumps to normotensive marmosets fed a low-sodium diet. Marmosets received a dose of 0.