Endothelin receptors are modulated in association with endogenous fluctuations in estrogen
D. A. Barber, G. C. Sieck, L. A. Fitzpatrick and V. M. Miller Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. Experiments were designed to determine whether endogenous physiological fluctuations in sex steroid hormones affect expression or functional responses of...
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Veröffentlicht in: | American journal of physiology. Heart and circulatory physiology 1996-11, Vol.271 (5), p.H1999-H2006 |
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Zusammenfassung: | D. A. Barber, G. C. Sieck, L. A. Fitzpatrick and V. M. Miller
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Experiments were designed to determine whether 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-labeled 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
inhibition constant) 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 with male pigs and
were not affected significantly by removal of the endothelium or by
treatment of the rings with either indomethacin (10(-5) mol/l) or the
combination of indomethacin and NG-monomethyl-L-arginine (10(-4) mol/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 with male pigs.
This phenomenon occurs at the level of smooth muscle and is not dependent
on the endothelium or synthesis of nitric oxide or prostaglandins. |
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ISSN: | 0363-6135 0002-9513 1522-1539 |
DOI: | 10.1152/ajpheart.1996.271.5.h1999 |