Role of endothelium in conversion of angiotensin I to angiotensin II in Rabbit aorta

Abstract

Rabbit aortic rings with either an intact endothelium or a disrupted endothelium were used to generate dose response curves to angiotensin I (AI) in the presence (EDM = 3 ×10-7 M) and absence (ED50 = 1.7 × 10-8 M) of 10 μg/ml teprotide, a converting-enzyme inhibitor. Treatment with teprotide did not alter responses to angiotensin II (All). Comparable dose-dependent responses were obtained with All regardless of endothelial integrity. Contraction velocities in response to angiotensin I (10-7 M) and All (10-7 M) were also measured. Angiotensin II produced a significantly greater contraction velocity (p <0.001) than that produced by AI. The amount of conversion to AH by both intact rabbit aortic rings and rings following removal of the endothelium was determined using125I-AI and IKI-AII. Waters C18 SEP-PAK columns were used to separate AI and All. During the first 3 to 4 minutes after the addition of AI, contraction velocity measurements and conversion were greater in intact rings than rings without endothelium. Conversion of AI to All in endothelial-disrupted rings was the same as in intact rings by 5 minutes after the addition of AI. Conversion of AI to AH was inhibited by 30 μg/ml teprotide at all times measured, and there was no evidence of an alternate route of metabolism. Angiotensin I contraction velocity measurements after 10 μg/ml teprotide also demonstrated impaired efficiency of conversion of AI to All. Thus, it was established that a lack of endothelium attenuated the rate of conversion of AI to All initially, and formation of AH with or without endothelium was blocked by teprotide. This evidence strongly suggests that the rates of conversion of AI to All are influenced by endothelial cells in the arterial wall, and AI has a weak direct action on vascular smooth muscle. © 1984 American Heart Association, Inc.