Analysis of responses to angiotensin I and angiotensin I-(3-10) in the mesenteric vascular bed of the cat.
Responses to angiotensin I and antiogensin I-(3-10), the precursors for angiotensin II and IV, were investigated in the mesenteric vascular bed of the cat. Under constant-flow conditions, injections of precursors and the active peptides into the mesenteric arterial perfusion circuit caused dose-related increases in receptor antagonist that were attenuated by the angiotensin AT1 receptor antagonist DuP532 (2-propyl-4-pentafluorethyl-1-[2'-(2H-tetrazol-5-YL)-1,1'-bi phenyl-4-YL methyl]1H-imidazole-5-carboxylic acid), but not by the angiotensin AT2 receptor antagonist PD123,319 ((S)1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl )-4,5,6,7- tetrahydro-1H-imadazo[4,5-c]pyridine-6-carboxylic acid, ditriflouroacetate]). Responses to angiotensin I and II were similar as were responses to angiotensin I-(3-10) and angiotensin IV, and these responses were not altered by the presence of a time-delay coil in the perfusion circuit. Responses to angiotensin I and angiotensin I-(3-10) were decreased by the angiotensin converting enzyme inhibitor enalaprilat in a dose of the angiotensin converting enzyme inhibitor that had no effect on responses to angiotensin II and IV and that enhanced vasodilator responses to bradykinin. The putative angiotensin AT2 receptor agonist, p-aminophenylalanine6-angiotensin II, produced dose-related increases in mesenteric arterial perfusion pressure that were reduced by DUP532, suggesting that they are mediated by angiotensin AT1 receptors. These results suggest that angiotensin I and angiotensin I-(3-10) are rapidly and efficiently converted by an angiotensin converting enzyme-dependent pathway into active peptides that induce vasoconstriction by activating angiotensin AT1 receptors in the mesenteric vascular bed of the cat.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Garrison
E A
EA
Estrada
L S
LS
Potter
J M
JM
Kadowitz
P J
PJ
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D013152:Splanchnic Circulation / Q000187:drug effects*
D000804:Angiotensin II; D000803:Angiotensin I; D001920:Bradykinin