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 AT 1 receptor antagonist DuP532 (2-propyl-4-pentafluoroethyl-1-[2′-(2 H-tetrazol-5-YL)-1, 1′-biphenyl-4-YL methyl]1 H-imidazole-5-carboxylic acid), but not by the angiotensin AT 2 receptor antagonist PD123,319 (( S)1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1 H-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 AT 2 receptor agonist, p-aminophenylalanine 6-angiotensin II, produced dose-related increases in mesenteric arterial perfusion pressure that were reduced by DUP532, suggesting that they are mediated by angiotensin AT 1 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 AT 1 receptors in the mesenteric vascular bed of the cat.