Characteristics of the blood pressure lowering action of renin inhibition and comparison with angiotensin converting enzyme inhibition

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Mean arterial blood pressure (MAP) was 100±4mmHg in a group (n=3) of conscious sodium-deficient dogs. A 3-day infusion of the renin inhibitor isovaleryl -His-Pro-Phe-His-Sta-Leu-Phe-NH2 (SCRIP) lowered MAP to an average of 79 ± 4 mmHg. Termination of the infusion resulted in a prompt rise in MAP to 100 ± 5mmHg but plasma renin activity (PRA), which was 22 ± 2 ng angiotensin (Ang) I/ml per h before the infusion, recovered only to 5 ± 1 ng Ang I/ml per h during the same time (4h after infusion). In other experiments in sodium-deficient dogs, a direct comparison was made between inhibition of PRA and the reduction of blood pressure. Over the dose range 0.1-2 μg/kg per min, PRA was inhibited in a dose-related manner, but MAP was not reduced. At dose levels beginning an order of magnitude higher (e.g. 20-160g/kg per min), PRA was completely inhibited and there was a dose-related fall in MAP. These data suggest that there is no correlation between inhibition of PRA and the reduction in blood pressure in chronically sodium-deficient dogs. In other studies comparing renin inhibition with angiotensin converting enzyme (ACE) inhibition, there was evidence for greater efficacy of ACE inhibition in conscious sodiumdeficient dogs, but no evidence of any difference in one-kidney, one clip hypertensive dogs.

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