Effects of a renin inhibitor, SR 43845, and of captopril on blood pressure and plasma active renin in conscious sodium-replete macaca


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Abstract

The effects of the renin inhibitor, SR 43845 (IC50=10-11 mol/l human and primate plasma renin) and of the angiotensin converting enzyme (ACE) inhibitor captopril on blood pressure and plasma active renin were investigated in conscious, chronically instrumented, sodium-replete macaca (cynomolgus monkeys). Perfusion of SR 43845 at 0.33, 3.3, 33, 100 and 200(μg/kg per min for 30min elicited a dose-related decrease in blood pressure with a notable effect on plasma renin activity (PRA; 90% inhibition), beginning at a dose of 0.33μg/kg per min. The maximal reduction in blood pressure of 22 ± 2mmHg (from 110 ± 5mmHg) was achieved at 100μg/kg per min and a higher dose (200(μg/kg per min) induced no further reduction. Plasma levels of active renin were also significantly increased (to 104%, from 102 ± 14pg/ml) at the lower dose. Captopril, tested at 33μg/kg per min under the same experimental conditions, lowered blood pressure in a similar manner and with the same intensity as the renin inhibitor at an equal dose (by 14 ± 1 mmHg, from 114 ± 4 mmHg). However, a dose six times as high only influenced the decrease of blood pressure slightly (by 16 ± 2 mmHg, from 103 ± 5 mmHg). For the same hypotensive effect, the plasma renin concentration was significantly higher with the renin than with the ACE inhibitor. The recovery of pre-infusion blood pressure was both time- and dose-dependent, the basal value being almost restored after 5h with both inhibitors, although the initial plasma renin levels were not completely recovered. A comparison of the maximal hypotensive effects and the plasma active renin concentrations elicited by the renin and the ACE inhibitors suggests that there are no major differences between the two types of inhibition and that renin inhibition is slightly more efficient.

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