[Mpr(14)]-rADM(14-50), a novel analog of adrenomedullin, possesses potent vasodilator activity in the hindlimb vascular bed of the cat

Responses to [Mpr(14)]-rADM(14-50), a novel analog of adrenomedullin, were investigated in the hindlimb vascular bed of the cat under conditions of controlled blood flow. Intraarterial injections of [Mpr(14)]-rADM(14-50) in doses of 0.003-1 nmol caused dose-related decreases in hindlimb perfusion pressure. In terms of relative vasodilator activity, [Mpr(14)]-rADM(14-50) was more potent than human synthetic adrenomedullin (hADM) in doses of 0.003-0.1 nmol. The recovery half-times (T1/2) for the vasodilator response to [Mpr(14)]-rADM(14-50) were significantly greater than the recovery half-times for hADM in all doses studied. Decreases in hindlimb perfusion pressure in response to [Mpr(14)]-rADM(14-50) were not altered by the calcitonin gene-related peptide receptor antagonist rCGRP(8-37) at the same time vasodilator responses to calcitonin gene-related peptide were significantly reduced. The present data demonstrate that [Mpr(14)]-(14-50) has potent and long-lasting vasodilator activity when compared to hADM, and that vasodilator responses to [Mpr(14)]-rADM(14-50) are not dependent on the activation of CGRP receptors in the hindlimb vascular bed of the cat.