Thrombin-induced vascular reactivity is modulated by etb receptor
-coupled nitric oxide release in rat aorta.
Magazine, Harold I., and Kamal D. Srivastava.
Department of Biology, Queens College and the Graduate School of
the City, University of New York, 65-30 Kissena Blvd., Flushing, New
York 11367, USA
APStracts 3:0083C, 1996.
The role of endothelin receptors in thrombin-induced modulation of
vascular tone was evaluated by direct measurement of endothelin-1 and
endothelin receptor-coupled nitric oxide release and developed
isometric tension in thrombin-treated aortic rings. Here we report
that rapid release of endothelin-1 and subsequent ETB receptor
activation is required for production of the potent vasodilator,
nitric oxide, by thrombin-stimulated aorta. Thrombin-induced nitric
oxide release is ablated by pretreatment with ETB receptor
antagonists or following ET receptor desensitization by repeated
stimulation with endothelin-1. Thrombin-induced relaxation of
precontracted vessels was abrogated in the presence of ETB receptor
antagonists and in contrast, marked contraction to thrombin was
observed. These data indicate that the endothelium-dependent
vasodilator activity previously attributed to thrombin is indirect
and requires ETB receptor-coupled NO release and suggests that ET
receptor modulation of thrombin-induced vascular tone may contribute
to the increased vasomotor tone observed in diseased and mechanically
injured vessels.
Received 22 January 1996; accepted in final form 7 March 1996.
APS Manuscript Number C38-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96