Endothelin-1 and nitric oxide release modulates contraction of rat
aorta to selected thrombin receptor agonists.
Magazine, Harold I., 0mar Butt, and Hooman R. Yaghoutiel.
Department of Biology, Queens College and Graduate School of the
City University of New York, and The Cardiac Research Center,
University Medical Center at the State University of New York at
Stony Brook, 65-30 Kissena Blvd, Flushing, NY, 11367
APStracts 3:0001C, 1996.
The contribution of endothelin-1 (ET-1) and nitric oxide release (NO)
to vascular contraction induced by synthetic peptide agonists of the
[alpha]-thrombin receptor (Trap-14, Trap-6) was evaluated using rings
of rat aorta. Trap-6 induced 4-fold greater contraction than that
induced by addition of Trap-14. Trap-14 but not Trap-6 stimulation of
aortic rings resulted in a rapid (sec) and dose-dependant increase in
ET-1 levels detected in the vessel perfusate. Release of ET-1 in
vessels denuded of endothelium was indistinguishable from that of
intact vessels, suggesting that endothelial cells are not required
for the observed ET-1 release. The contractile potency of Trap-14 was
reduced in the presence of BQ-123, a specific antagonist of the ETA
subtype of ET receptors, whereas Trap-14 potency was increased
significantly by pretreatment with the nitric oxide synthetase
inhibitor, L-NNA. The contractile potency of Trap-6 was not altered
in the presence of BQ-123 or L-NNA, suggesting that Trap-14 but not
Trap-6 potency is modulated by ET-1 and NO release. These data
indicate that Trap-6 has limited function relative to Trap-14 and
that thrombin receptor activation is not sufficient to induce ET-1
and NO release from rat aorta.
Received 13 September 1995; accepted in final form 5 February
1995.
APS Manuscript Number C554-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96