Angiotensin formation in the isolated rat hindlimb.

Local vascular generation of angiotensin was investigated in isolated perfused rat hindquarters. Extraction and combined high-performance liquid chromatography (HPLC)/radioimmunoassay analysis of hindlimb perfusate showed a spontaneous release of angiotensin I (Ang I; 5.0 +/- 3.4 fmol/h) and angiotensin II (Ang II; 31.8 +/- 7.9 fmol/h). Angiotensin converting enzyme (ACE) inhibition with captopril abolished Ang II release while Ang I levels increased more than 10-fold. Perfusion with purified hog renin caused a dose-dependent angiotensin release and vasoconstriction. The renin inhibitor H-142 abolished all effects of renin whereas ACE inhibition prevented Ang II formation and vasoconstriction but increased Ang I levels. Metabolism and pressor effects of synthetic tetradecapeptide renin substrate (TDP), Ang I and Ang II were studied using a recirculating rat hindlimb perfusion system. TDP-dependent formation of Ang I and II, and an increase in perfusion pressure was shown; ACE inhibition reduced but did not abolish Ang II formation and vasoconstriction. Ang I was converted to Ang II by about 50% during one pass through a hindlimb. This conversion was abolished by ACE inhibition. These data add support to the presence of a functional vascular renin-angiotensin system.