Endothelin receptors are modulated in association with endogenous
fluctuations in estrogen.
Barber, Dustan A., Gary C. Sieck, Lorraine A. Fitzpatrick, and
Virginia M. Miller.
Departments of Surgery, Anesthesiology and Medicine, Mayo Clinic
and Foundation, Rochester, MN
APStracts 3:0148H, 1996.
Experiments were designed to determine whether or not endogenous
physiological fluctuations in sex steroid hormones affect expression
or functional responses of endothelin-receptors. Coronary arteries
from sexually mature male, female and ovariectomized pigs were
prepared either for receptor binding or measurement of isometric
force in organ chambers. Competitive binding of 125I-endothelin-1 was
significant for a one-site model with unlabeled endothelin-1 and a
two-site model with unlabeled endothelin-3 and sarafotoxin S6c in all
pigs. The total number of binding sites for all endothelin ligands
was not different between male and female pigs. Binding affinities
for the high affinity binding site for both endothelin-3 and
sarafotoxin S6c were significantly greater (lower Ki) in membranes
prepared from female pigs with high endogenous estrogen. In organ
chamber experiments, contractions to endothelin-1 but not endothelin
-3 or sarafotoxin S6c were significantly greater in coronary arterial
rings from female compared to male pigs and were not affected
significantly by removal of the endothelium or by treatment of the
rings with either indomethacin (10-5 moles/L) or the combination of
indomethacin and NG-monomethyl-L-arginine (10-4 moles/L). These
results suggest endogenous fluctuations in estrogen are associated
with an increase in affinity of a high affinity endothelin-receptor
in coronary arterial smooth muscle of female pigs. In addition,
independent of endogenous estrogen status, coronary arteries from
female pigs generate significantly greater contractions to
endothelin-1 compared to male pigs. This phenomena occurs at the
level of smooth muscle and is not dependent upon the endothelium or
synthesis of nitric oxide or prostaglandins.
Received 1 November 1995; accepted in final form 1 April 1996.
APS Manuscript Number H1028-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 16 April 96