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.
Hilgers
K F
KF
Department of Internal Medicine, University of Heidelberg, Federal Republic of Germany.
Kuczera
M
M
Wilhelm
M J
MJ
Wiecek
A
A
Ritz
E
E
Ganten
D
D
Mann
J F
JF
D000803:Angiotensin I / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006614:Hindlimb / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D012083:Renin