Effects of a novel renin inhibitor in patients with essential hypertension.
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.
Bursztyn
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Department of Medicine, Boston University School of Medicine, Massachusetts 02118.
Gavras
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Tifft
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Luther
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Boger
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Gavras
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D000328:Adult; D001774:Blood Chemical Analysis; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D004151:Dipeptides / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011674:Pulse / Q000187:drug effects; D012083:Renin / Q000097:blood; D000092502:Renin Inhibitors
D002216:Captopril; D003404:Creatinine; D004151:Dipeptides; D012083:Renin; D000092502:Renin Inhibitors; C056622:enalkiren