Proadrenomedullin nh2-terminal 20 peptide has direct vasodilator
activity in the cat.
Champion, Hunter C., William A. Murphy, David H. Coy, and Philip J.
Kadowitz.
Departments of Pharmacology and Medicine, Tulane University School
of Medicine, New Orleans, LA 70112
APStracts 3:0366R, 1996.
The mechanism by which proadrenomedullin NH2-terminal 20 peptide
(PAMP) decreases vascular resistance was investigated in the hindlimb
vascular bed in the cat. Injections of PAMP, a shortened form of the
peptide PAMP(12-20), and adrenomedullin (ADM) into the hindlimb
perfusion circuit elicit dose-related decreases in perfusion
pressure. The order of potency was ADM > PAMP >
PAMP(12-20), and the calcitonin gene-related receptor peptide (CGRP)
receptor antagonist, CGRP(8-37), was without effect on vasodilator
responses to PAMP or ADM. Vasodilator responses to PAMP were
increased in duration by the cAMP phosphodiesterase inhibitor,
rolipram, whereas inhibitors of nitric oxide synthase and cGMP
phosphodiesterase were without effect. Vasodilator responses to PAMP
were not altered by treatment with alpha receptor or adrenergic nerve
terminal blocking agents and were similar in innervated and
denervated hindlimb preparations. Responses to PAMP were similar when
vasoconstrictor tone was increased by stimulation of the sympathetic
nerves or infusion of phenylephrine and were not altered by the
passage of time. These data suggest that PAMP dilates the hindlimb
vascular bed by a direct cAMP-dependent mechanism, and that
inhibition of norepinephrine release plays little if any role in
mediating responses to the peptide in the regional vascular bed of
the cat.
Received 3 July 1996; accepted in final form 1 October 1996.
APS Manuscript Number R382-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996