Role of converting enzyme in the responses of rabbit atria, aortas, and adrenal zona glomerulosa to [des-Asp1]angiotensin I.
- 1 August 1977
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 41 (2), 231-238
- https://doi.org/10.1161/01.res.41.2.231
Abstract
Conversion of angiotensin I (A I) and [des-Asp1]angiotensin I (des1-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 [des1-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 A I and des1-A I by the enzyme preparation was studied. Angiotensin I and des1-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 des1-A I without significantly altering responses to A II and A III. The steroidogenic activity of A I and des1-A I in adrenal cells was dependent on conversion since treatment with CEI specifically abolished aldosterone biosynthesis induced by A I and des1-A I without changing the activities of A II or A III. The Km values for A I and des1-A I determined with lung enzyme were 80 .mu.M and 30 .mu.M, respectively. The hydrolysis of A I and des1-A I was competitively inhibited by CEI, A II and A III. Angiotensin III was the most potent CEI among several metabolites of A I. Apparently des1-A I was a better substrate than A I for isolated pulmonary converting enzyme. Purified and tissue converting enzymes rapidly converted des1-A I. The data are consistent with the postulated alternative pathway for formation of A III from des1-A I subsequent to N-terminal degradation of A I.This publication has 24 references indexed in Scilit:
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