Adrenomedullin(22-52) antagonizes vasodilator responses to
calcitonin gene-related peptide but not adrenomedullin in the
cat.
Champion, Hunter C., Jos[acute]e A. Santiago, William A. Murphy, David
H. Coy, and Philip J. Kadowitz.
Departments of Pharmacology and Medicine, Tulane University School
of Medicine, New Orleans, Louisiana 70112
APStracts 3:0290R, 1996.
The effects of adrenomedullin (ADM) (22-52), a putative ADM receptor
antagonist, on vasodilator responses to ADM and the structurally
-related peptide, calcitonin gene-related peptide (CGRP), were
investigated in the hindlimb vascular bed of the cat under constant
-flow conditions. ADM(22-52) had no significant effect on hindlimb
perfusion pressure when injected in doses up to 120 nmol; and,
following administration of ADM(22-52), vasodilator responses to ADM
were unchanged, whereas vasodilator responses to CGRP were inhibited.
The inhibitory effects of ADM(22-52) on responses to CGRP were
selective and reversible and were similar to the inhibitory effects
of the CGRP antagonist, CGRP(8-37). Hindlimb vasodilator responses to
CGRP and to ADM were increased in duration by the cAMP
phosphodiesterase inhibitor, rolipram, but were not altered by
inhibitors of cGMP phosphodiesterase, nitric oxide synthetase, K+ATP
channels, the cyclooxygenase pathway, or the adrenergic nervous
system. These results demonstrate that ADM(22-52) is a selective CGRP
receptor antagonist in the hindlimb vascular bed of the cat. The
present data suggest that vasodilator responses to CGRP and ADM are
mediated by different receptors, but that these peptides dilate the
hindlimb vascular bed of the cat by a similar cAMP-dependent
mechanism.
Received 10 April 1996; accepted in final form 8 July 1996.
APS Manuscript Number R205-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996