Role of converting enzyme in the responses of rabbit atria, aortas, and adrenal zona glomerulosa to [des-Asp1]angiotensin I.

Abstract

SUMMARY Conversion of angiotensin I (A I) and [des-Asp' |angiotensin I (des'-A I) to angiotensin II (A II) and angiotensin III (A III), respectively, was studied in aortic strips, left atria, adrenal zone glomerulosa cell suspensions from rabbits, and with purified rabbit lung converting enzyme. Conversion of A I and [des'-A I] was estimated in the presence and absence of Bothrops jararaca nonapeptide, converting enzyme inhibitor (CEI), by measuring the changes in peptide-induced tension development in aortas and atria and on steroidogenesis in cell suspensions. The liberation of histidyl-leucine from AI and des'-A I by the enzyme preparation was studied. Angiotensin I and des'-A I possessed 23% and 1% contractile activity (aorta), and 34% and 4% positive inotropic activity (atria), respectively, when compared to A II. Inhibition of aortic and atrial converting enzymes attenuated responses to A I and des'-A I without significantly altering responses to AH and A HI. The steroidogenic activity of AI and des'-A I in adrenal cells was dependent on conversion since treatment with CEI specifically abolished aldosterone biosynthesis induced by AI and des'-A I without changing the activities of A II or A III. The Km values for AI and des'-A I determined with lung enzyme were 80 /IM and 30 /IM, respectively. The hydrolysis of A I and des'-A I was competitively inhibited by CEI, A II, and A HI. Angiotensin III was the most potent CEI among several metabolites of A I. These results indicate that des'-A I was a better substrate than A I for isolated pulmonary converting enzyme. The present investigation clearly indicates that des'-A I is rapidly converted by purified and tissue converting enzymes. The data are consistent with the postulated alternative pathway for formation of A HI from des'-A I subsequent to N-terminal degradation of A I.