Analysis of responses to angiotensin I-(3-10) in the hindlimb vascular bed of the cat.
Responses to angiotensin I-(3-10), the precursor for angiotensin IV, were investigated in the anesthetized cat. Intravenous injections of the precursor caused dose-related increases in systemic arterial pressure that were similar to responses elicited by angiotensin i.v. and that were inhibited by captopril. in the hindlimb vascular bed of the cat under constant-flow conditions, injections of the substrate into the perfusion circuit in doses of 3-100 micrograms caused dose-related increases in hindlimb perfusion pressure that were rapid in onset and were not altered by the presence of a time-delay coil in the perfusion circuit. Dose-response curves for the precursor and angiotensin i.v. were parallel, and the precursor was approximately twofold less potent than angiotensin i.v. in its ability to increase hindlimb perfusion pressure. Responses to the precursor were inhibited by captopril in a dose that attenuated hindlimb vasoconstrictor responses to angiotensin I. Increases in hindlimb perfusion pressure in response to angiotensin I-(3-10) were inhibited by DuP-532 in a dose that attenuated the response to angiotensin i.v. PD-123,319, an AT2 receptor antagonist, had no significant effect on responses to angiotensin I-(3-10). The present results suggest that angiotensin I-(3-10) is rapidly and efficiently converted by an angiotensin converting enzyme-dependent pathway into an active peptide, which induces vasoconstriction by activating AT1 receptors in the peripheral vascular bed of the cat.
Garrison
E A
EA
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Kadowitz
P J
PJ
D000803:Angiotensin I / Q000031:analogs & derivatives*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000098:blood supply*; D011945:Receptors, Angiotensin / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction
D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D000803:Angiotensin I; D002216:Captopril