Vascular effects and metabolism of angiotensins and their metabolites in the isolated perfused rat kidney.

The vascular effects of the injection of angiotensin I (AI), des-Asp1-angiotensin I (des-Asp1-AI), angiotensin II (AII), des-Asp1-angiotensin II ( (2-8)AII) and des-Asp1-Arg2-angiotensin II ( (3-8)AII) have been investigated in an isolated perfused rat kidney model, using a closed circuit system. The apparent half-life of these peptides was measured by AI and AII radioimmunoassays. Des-Asp1-AI is less potent than AI and has a shorter duration of action on perfusion pressure and renal flow. Up to 7.6% of circulating AI and 12.4% of circulating des-Asp1-AI are converted by the kidney to AII, (2-8)AII and other AII immunoreactive materials. This intrarenal conversion entirely explains the vasoconstrictor effects of these two peptides. The vasoconstrictor effects of (2-8)AII is similar to that of AII, but (2-8)AII has a shorter duration of action. At the doses injected, renin secretion is completely inhibited by AII and (2-8)AII, it is partially inhibited by AI, an effect which disappears when converting enzyme is inhibited. Des-Asp1-AI is a less potent inhibitor of renin secretion than AI, and (3-8)AII is devoid of any action on renin secretion. The apparent half-life of AI is 24.3 +/- 1.1 minutes, des-Asp1-AI: 20 to 23 minutes, AII: 19.6 +/- 1.8 minutes, (2-8)AII: 12 to 14.5 minutes and (3-8)AII: 12.5 to 13.5 minutes. Differences in the metabolism of these peptides may contribute to the differences of magnitude and duration of their vascular effects.