Functional comparison of endothelin receptors in human and rat
pulmonary artery smooth muscle.
Bialecki, Russell A., Carol S. Fisher, Wallace W. Murdoch, Herbert G.
Barthlow, and Darci L. Bertelsen.
Respiratory, Inflammatory and Neurological Diseases Research
Section, ZENECA Pharmaceuticals, A business unit of ZENECA, Inc.,
Wilmington, DE 19850-5437
APStracts 3:0179L, 1996.
The receptors mediating arterial smooth muscle contraction to
endothelins (ET) differ among species and origin of vascular bed. We
characterized ET receptors mediating contraction of endothelium
-denuded human intralobar pulmonary artery (hIPA), rat intralobar
(rIPA) and extralobar left branch pulmonary artery (rLPA) with ET-1,
-2, -3, sarafotoxin 6c (S6c), S6b, and ET receptor antagonists in
vitro. Rat aorta was studied for comparison. Each vascular segment
showed concentration-dependent contraction with a rank order
sensitivity (pD2) profile of ET-1>ET-2=S6b>ET-3.
Maximum contraction to ET-1 was greater than to S6c in all
preparations. Responses of rIPA and rLPA to S6c were conspicuous when
compared with hIPA or aorta. The ETA receptor blockers, BQ-123 and
BMS-182874, competitively antagonized ET-1 responses of hIPA and
aorta, but not rLPA. The ETB receptor antagonist, BQ-788, attenuated
contractions of rIPA and rLPA to ET-3 and S6c, respectively. In
conclusion, ETB-mediated contraction of endothelium-denuded conduit
pulmonary arteries varies among species and may contribute more to
contraction of rIPA and rLPA than of hIPA and aorta, although maximum
ETB-mediated contraction is smaller than that mediated by the ETA
receptor.
Received 3 April 1996; accepted in final form 3 October 1996.
APS Manuscript Number L110-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996