Inhibition of converting enzyme of the renin-angiotensin system in kidneys and hindlegs of dogs.

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 2a but the effects of bradykinin were potentiated. KEY WORDS angiotensin I angiotensin II iliac blood flow converting enzyme inhibitor Bothrops jararaca peptides renal blood flow bradykinin • During intra-arterial infusions of angio-tensin I (AI) or angiotensin II (All), 60-90% of the biological activity of the peptides disappears in one passage through renal or hindlimb vascular beds of dogs (1, 2). Ng and Vane (1) discussed the possibility that some of the AI which disappeared in kidneys or hindlegs may first have been converted to All and the All then destroyed before its activity could be detected in the venous output. However, because AI was much less potent than All in reducing hindlimb or renal blood flow when injected intra-arterially, they concluded that there was little or no angiotensin-converting enzyme activity in these two peripheral vascular beds and that, as shown previously (3), the lungs were the most important site for converting blood-borne AI to AIL Franklin et al. (4), however, found intra-arterial AI to be more potent in reducing renal blood flow of dogs than originally reported by Ng and Vane (1), and further studies (5) suggest that this activity of AI in the kidney was …