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 ×s 1.1 minutes, des-Asp¹-AI: 20 to 23 minutes, AII : 19.6 ×s 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.