[MPR14]-rADM(14-50), a novel analog of adrenomedullin, possesses potent vasodilator activity in the hindlimb vascular bed of the cat.
Responses to [Mpr14]-ADM(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 [Mpr14]-rADM(14-50) in doses of 0.003-1 nmol caused dose-related decreases in hindlimb perfusion pressure. In terms of relative vasodilator activity, [Mpr14]-rADM(14-50) was more potent than human synthetic adrenomedullin (hADM) in doses of 0.003-0.1 nmol. The recovery half-times (T 1/2) for the vasodilator response to [Mpr14]-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 [Mpr14]-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 [Mpr14]-(14-50) has potent and long-lasting vasodilator activity when compared to hADM, and that vasodilator responses to [Mpr14]-rADM(14-50) are not dependent on the activation of CGRP receptors in the hindlimb vascular bed of the cat.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Duperier
C D
CD
Fitzgerald
W E
WE
Lambert
D G
DG
Murphy
W A
WA
Coy
D H
DH
Kadowitz
P J
PJ
D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb / Q000187:drug effects*; D006801:Humans; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide