Abstract
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 0.3 (n = 5), 3.0 (n = 5), or 30 (n = 6) mg/kg/day for 14 days. Blood pressure (BP) and heart rate (HR) were measured in conscious animals by the tail-cuff method. Plasma renin activity (PRA) was reduced by 68% and 84%, respectively, by the 0.3 and 3.0 mg/kg/day doses. However, these doses had no significant effect on BP. Plasma-renin activity was reduced by 93% after 2 days of administration of the 30 mg/kg/day dose, and BP was significantly reduced (-24 +/- 4 mm Hg). After 14 days, PRA had recovered to pretreatment levels, but the hypotensive response persisted (-20 +/- 3 mm Hg). Despite the fall in BP, HR was not increased (292 +/- 22, 283 +/- 16, and 267 +/- 8 beats/min on days 0, 2, and 14, respectively). These findings indicate that, after 2 days of continuous administration, a dose of CGP 29,287 that induces almost complete inhibition of PRA is required to induce a significant fall in BP. Although there is subsequent recovery of ...Continue Reading
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