Conversion of angiotensin I to angiotensin II in dog isolated renal artery: role of two different angiotensin II-generating enzymes.
The functional role of the endothelium in conversion of angiotensin (Ang) I to Ang II was studied in helical strips of dog renal arteries. In the arteries precontracted with PGF2 alpha, Angs I and II caused a moderate relaxation, which was abolished by treatment with saralasin and reversed to a contraction by indomethacin. Removal of the endothelium attenuated the response to Ang I but did not abolish it. The Ang I-induced relaxation in the arteries without endothelium was not significantly attenuated by an Ang-converting enzyme inhibitor, SA446, but was markedly suppressed by chymostatin. On the other hand, in the arteries with endothelium, the relaxation was suppressed but not abolished by SA446, and the remaining relaxation was abolished by additional treatment with chymostatin. Relaxation induced by prostaglandin I2 was unaffected by these enzyme inhibitors. These results strongly suggest that the conversion of Ang I to Ang II is due mainly to the Ang-converting enzyme in the endothelium and to the chymostatin-sensitive Ang II-generating enzyme in subendothelial tissues.
Department of Pharmacology, Shiga University of Medical Sciences, Seta, Japan.
T
T
Okamura
H
H
Okunishi
K
K
Ayajiki
N
N
Toda
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000096:biosynthesis* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D009842:Oligopeptides / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012077:Renal Artery / Q000201:enzymology; D012697:Serine Endopeptidases / Q000378:metabolism*; D053778:Thiazolidines; D014191:Tranylcypromine / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D053778:Thiazolidines; D000804:Angiotensin II; D014191:Tranylcypromine; D000803:Angiotensin I; C002101:chymostatin; D015097:3-Mercaptopropionic Acid; D015237:Dinoprost; C033437:rentiapril; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; C054542:chymostatin-sensitive angiotensin II-generating enzyme; D007213:Indomethacin