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

Journal of Cardiovascular Pharmacology
J M WoodD Neisius

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

Citations

Sep 1, 1994·Journal of Clinical Pharmacology·W H FrishmanC Dike
Jan 1, 1994·Pharmacology & Therapeutics·J M WoodJ Maibaum
Oct 1, 1995·Cardiovascular Drugs and Therapy·H D Kleinert
Jun 26, 2012·Expert Opinion on Drug Safety·Fabio AngeliPaolo Verdecchia
Apr 18, 2008·European Journal of Pharmacology·Dilek IusufAnton J M Roks
Jul 1, 1990·Hypertension·P CorvolJ Ménard
Jun 13, 2002·The Journal of Toxicological Sciences·Ikuo HoriiKeitaro Hashimoto
Sep 15, 1988·Klinische Wochenschrift·K G Hofbauer, J M Wood
Jan 1, 1989·Fundamental & Clinical Pharmacology·P Corvol, J Menard
Apr 1, 1990·Medicinal Research Reviews·W J Greenlee
May 1, 1996·American Heart Journal·C Lin, W H Frishman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.