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.
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