ROLE OF ENDOTHELIUM IN CONVERSION OF ANGIOTENSIN-I TO ANGIOTENSIN-II IN RABBIT AORTA

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 of (ED50 = 3 .times. 10-7 M) and absence (ED50 = 1.7 .times. 10-8 M) of 10 .mu.g/ml teprotide, a converting-enzyme inhibitor. Treatment with teprotide did not alter responses to angiotensin II (AII). Comparable dose-dependent responses were obtained with AII regardless of endothelial integrity. Contraction velocities in response to angiotensin I (10-7 M) and AII (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 AII by both intact rabbit aortic rings and rings following removal of the endothelium was determined using 125I-AI and 125I-AII. Waters C18 SEP-PAK columns were used to separate AI and AII. During the first 3-4 min after the addition of AI, contraction velocity measurements and conversion were greater in intact rings than rings without endothelium. Conversion of AI to AII in endothelial-disrupted rings was the same as in intact rings by 5 min after the addition of AI. Conversion of AI to AII was inhibited by 30 .mu.g/ml teprotide at all times measured, and there was no evidence of an alternate route of metabolism. Angiotensin I contraction velocity measurements after 10 .mu.g/ml teprotide also demonstrated impaired efficiency of conversion of AI to AII. Thus, it was established that a lack of endothelium attenuated the rate of conversion of AI to AII initially, and formation of AII with or without endothelium was blocked by teprotide. Apparently, the rates of conversion of AI to AII are influenced by endothelial cells in the arterial wall, and AI has a weak direct action on vascular smooth muscle.