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 TV 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 mu g caused dose-related increases in hindlimb perfusion press 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 TV were parallel, and the precursor was approximately twofold less potent than angiotensin TV 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 IV. PD-123,319, an AT(2) 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 AT(1) receptors in the peripheral vascular bed of the cat.