The endothelin-a receptor antagonist bq610 blocks cigarette smoke
induced mitogenesis in rat airways and vessels.
Dadmanesh, F., and J. L. Wright.
Department of Pathology, University of British Columbia
APStracts 3:0217L, 1996.
To ascertain whether endothelin may play a role in cigarette smoke
induced cell proliferation in the airways and arterial vasculature of
the lung, we exposed groups of 7 Sprague Dawley rats to either room
air (control) plus saline infusion, an intravenous infusion of the
selective endothelin A antagonist BQ610 (control BQ610), the smoke of
10 cigarettes (smoke only), or the smoke of 10 cigarettes after
intravenous BQ610 infusion (smoke BQ610). Cell proliferation was
identified by the BrdU cell labelling technique, and the percentage
of labelled cells calculated in the epithelium and wall components of
the bronchioles, and endothelium and wall components of the
peribronchiolalar and perialveolar ductular arteries. We found that
cigarette smoke produced significant cell proliferation in the airway
epithelium and wall, peribronchiolar arterial endothelial
compartment, and in both the endothelial and wall compartments of the
perialveolar ductular arteries. Pretreatment with BQ610 reduced the
peribronchiolar arterial endothelial and the perialveolar ductular
arterial wall proliferation to control levels, and reduced but did
not totally abrogate the smoke induced proliferation of the airway
epithelial, airway wall, and perialveolar ductular arterial
endothelial compartments. We conclude that cigarette smoke induced
cell proliferation of the airways and pulmonary arterial vessels is
at least partially mediated through stimulation of the endothelin A
receptors.
Received 22 July 1996; accepted in final form 6 November 1996.
APS Manuscript Number L231-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996