Formation of angiotensin III from [des-Asp1]angiotensin I in the mesentric vasculature.
The effects of [des-Asp1]angiotensin I and angiotensin III on mesenteric blood flow were compared in 15 pentobarbital-anesthetized dogs. These agonists were administered as bolus injections directly into the vasculature supplied by the superior mesenteric artery. Both [des-Asp1]angiotensin I and angiotensin III produced dose-dependent decreases in mesenteric blood flow, with angiotensin III being more potent than [des-Asp1]angiotensin I at all doses tested. The constrictor responses to [des-Asp1]angiotensin I were markedly attenuated in the presence of an angiotensin-converting enzyme inhibitor (SQ20881); SQ20881 did not alter responses to angiotensin III or norepinephrine. The administration of [Ile7]angiotensin III (an angiotensin III antagonist) attenuated the responses to both [des-Asp1]angiotensin I and angiotensin III, without altering the responses to norepinephrine. These results suggest that the decrease in mesenteric blood flow produced by [des-Asp1]angiotensin I is largely caused by its local enzymatic conversion to angiotensin III. This conversion in one transit through the mesenteric vasculature is approximately 24%.
D000803:Angiotensin I / Q000031:analogs & derivatives / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives*; D000805:Angiotensin III / Q000096:biosynthesis* / Q000494:pharmacology; D000809:Angiotensins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D008643:Mesentery / Q000098:blood supply; D012039:Regional Blood Flow / Q000187:drug effects; D013722:Teprotide / Q000494:pharmacology; D014662:Vasoconstrictor Agents
D000809:Angiotensins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000805:Angiotensin III; D000803:Angiotensin I; D013722:Teprotide