Adrenomedullin activity in the chronically hypoxic rat lung.
Zhao, Lan, Lesley A. Brown, Ali A. Owji, Derek J. Nunez, David M.
Smith, Mohammad A. Ghatei, Stephen R. Bloom, and Martin R. Wilkins.
Department of Clinical Pharmacology and the Endocrine Unit,
Department of Medicine, Royal Postgraduate Medical School,
Hammersmith Hospital, Du Cane Road, London, W12 ONN
APStracts 3:0057H, 1996.
Adrenomedullin (AM) is a novel vasodilator with structural
similarities to calcitonin-gene-related peptide (CGRP). This study
investigated AM activity in the rat lung during hypoxia-induced
pulmonary hypertension. Both rat AM (0.2 to 10nmol) and [alpha]CGRP
(0.2 to 2nmol) produced dose-related reductions in pulmonary artery
pressure in the isolated perfused lung ventilated with 2% O2.
Pretreatment with [alpha]CGRP, which demonstrated tachyphylaxis, or
its antagonist, CGRP(8-37), reduced the hypotensive response to AM,
suggesting that part of the response to AM is mediated by CGRP
receptors. 125I-AM and 125I-CGRP binding was significantly increased
in lung membranes from 7 day hypoxic animals (AM from 1.94+/-0.3 to
3.36+/-0.4 and CGRP from 0.06+/-0.01 to 0.12+/-0.02 pmol.mg-1
protein), with no change in dissociation constant. Moreover, the
hypotensive response to both peptides was increased in the lungs of 7
day hypoxic rats. There was no significant change in lung
immunoreactive AM concentrations (hypoxic 5.04+/-0.48 versus control
6.28+/-0.76 pmol.g-1 wet weight of tissue) or steady-state AM mRNA
levels in 7 day hypoxic rats. Nonetheless, AM may be useful for the
acute pharmacological manipulation of pulmonary artery pressure in
hypoxia-induced pulmonary hypertension.
Received 28 August 1995; accepted in final form 24 January 1996.
APS Manuscript Number H806-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96