Characteristics of the blood pressure lowering action of renin inhibition and comparison with angiotensin converting enzyme inhibition.
Mean arterial blood pressure (MAP) was 100 +/- 4 mmHg 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 +/- 5 mmHg but plasma renin activity (PRA), which was 22 +/- 2 ng angiotensin (Ang) l/ml per h before the infusion, recovered only to 5 +/- 1 ng Ang l/ml per h during the same time (4 h 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 micrograms/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. 20-160 g/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 sodium-deficient dogs, but no evidence of any difference in one-kidney, one clip hypertensive dogs.
Blaine
E H
EH
Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63119.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000172:deficiency; D000092502:Renin Inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D012083:Renin; D012964:Sodium; D000092502:Renin Inhibitors; C041553:renin inhibitory peptide, statine