Acute and chronic effects of renin inhibitor GR70982 in the conscious marmoset

Abstract

The effects on plasma renin activity (PRA), mean arterial blood pressure (MABP) and heart rate (HR) of GR70982, a low molecular weight inhibitor of human renin, were studied in conscious marmosets. In vitro, GR70982 is a potent and selective inhibitor of human plasma renin (concentration producing 50% inhibition (IC 50): human renin = 6.9 × 10 −9 M; porcine pepsin and bovine cathepsin D = > 10 −3 M). In normotensive marmosets, i.v. GR70982 (0.001–0.1 mg kg −1) produced a dose-related inhibition of PRA. Larger oral doses (0.2, 1 and 5 mg kg −1) were required to achieve similar effects. In renin-dependent hypertensive marmosets, i.v. GR70982 (0.01 and 0.5 mg kg −1) produced dose-related decreases in MABP (−12 and −18 mm Hg) and PRA (−93 and −100%), with only minimal effects on HR. A 7-day continuous i.v. infusion of GR70982 (0.36 mg kg −1 day −1) in sodium-deplete marmosets produced a gradual decrease in MABP (−17 mm Hg at day 7, cf. control), accompanied by an inhibition of PRA (approximately 75%) and minimal HR effects.