Analysis of responses to human synthetic adrenomedullin and calcitonin gene-related peptides in the hindlimb vascular bed of the cat

Abstract

Vasodilator responses to human adrenomedullin (hADM), a newly discovered hypotensive peptide, human calcitonin gene-related peptide-α (hCGRP-α) and hCGRP-β, which share structural homology with hADM, were compared in the hindlimb vascular bed of the cat under constant flow conditions. Injections of hADM (0.003–1 nmol), hCGRP-α, and hCGRP-β (0.003–0.3 nmol) into the perfusion circuit caused dose-related decreases in hindlimb perfusion pressure. Vasodilator responses to hCGRP-α and hCGRP-β were similar in potency and duration, and the doses of hCGRP-α and hCGRP-β required to reduce hindlimb perfusion pressure 40 mm Hg (ED₄₀ mm Hg) were significantly lower than the ED₄₀ mm Hg for hADM. The duration of the hindlimb vasodilator responses to hCGRP-α and hCGRP-β were significantly longer than the duration of the response to hADM. Amylin, a peptide that shares structural homology with ADM and with CGRP, had no significant effect on hindlimb perfusion pressure when injected in doses up to 1 nmol. Decreases in hindlimb perfusion pressure in response to hADM, hCGRP-α, and hCGRP-β were not altered by L-N⁵-(1-iminoethyl)-ornithine (L-NIO) in a dose of the nitric oxide synthase inhibitor that decreased the vasodilator response to acetylcholine or by the cyclooxygenase inhibitor, meclofenamate, in a dose that decreased the vasodilator response to archidonic acid. The present data demonstrate that hADM, hCGRP-α, and hCGRP-β have potent, but relatively short-lasting, vasodilator activity, and that vasodilator responses are not dependent on the release of nitric oxide or vasodilator prostaglandins in the hindlimb vascular bed of the cat. (Mol Cell Biochem 176: 5–11, 1997)