Inhibition of Converting Enzyme of the Renin-Angiotensin System in Kidneys and Hindlegs of Dogs

Abstract

The activity of angiotensin-converting enzyme in hindlegs and kidneys was compared in anesthetized dogs. Intra-arterial injections of angiotensin I or angiotensin II to one kidney or one hindleg caused dose-dependent decreases in blood flow in that vascular bed. An inhibitor of angiotensin-converting enzyme activity did not affect the vasoconstrictor activity of angiotensin II but substantially reduced that of angiotensin I. The reduction in vasoconstrictor activity of angiotensin I during enzyme inhibition was used to calculate conversion of angiotensin I to angiotensin II. There was 40% conversion in hindleg but only 2.1% in kidney. After intra-arterial injection of angiotensin I, bioassay of angiotensin II in the renal or iliac venous blood indicated that 60-90% of freshly formed angiotensin II was inactivated before leaving the kidney or hindleg. The results show that converting enzyme activity is much greater in hindlegs than in kidneys and that the endogenously formed angiotensin II following intra-arterial injection of angiotensin I is destroyed to the same extent as intra-arterially injected angiotensin II. Intra-arterial infusion of the enzyme inhibitor increased hindleg blood flow in half of the dogs; renal blood flow increased in only one dog. The inhibitor did not affect vascular responses produced by norepinephrine, histamine, vasopressin, or prostaglandin F 2α but the effects of bradykinin were potentiated.