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J Cardiovasc Pharmacol. 1990 Mar;15(3):493-500.

Effects of a novel renin inhibitor in patients with essential hypertension.

Author information

1
Department of Medicine, Boston University School of Medicine, Massachusetts 02118.

Abstract

The effects of A-64662, a new specific renin inhibitor, on plasma renin activity (PRA) and blood pressure (BP) were studied for the first time in patients with essential hypertension. A single intravenous bolus of vehicle, 0.001, 0.003, 0.01, 0.03, and 0.1 mg/kg was given to the first four patients, maintained on a constant 100 mEq Na diet. PRA was promptly reduced from 3.4 +/- 2.9 (mean +/- SEM) to 0.2 +/- 0.06 ng/ml/h, a 94% inhibition with the smallest dose, and to undetectable levels (less than 0.1 ng/ml/h) with the larger ones. However, BP did not change within this dose range. The subsequent seven patients received larger doses ranging from 0.2 to 1.0 mg/kg. In three cases, there was reduction in BP on the second dosing day, at doses of 0.4, 0.7, and 1 mg/kg. All responses were late (at 110 min after the injection), transient, and unrelated to baseline PRA. These results strongly suggest that there is a dissociation between the effectiveness of A-64662 in inhibiting PRA and its blood pressure lowering effect in hypertensive patients.

PMID:
1691375
[Indexed for MEDLINE]

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