Endothelin receptors are modulated in association with endogenous fluctuations in estrogen

Dustan A. Barber, Gary C. Sieck, Lorraine A. Fitzpatrick, Virginia M. Miller

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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 N(G)-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.

Original languageEnglish (US)
Pages (from-to)H1999-H2006
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume271
Issue number5 40-5
DOIs
StatePublished - Nov 1996

Keywords

  • 17β-estradiol
  • coronary artery
  • endothelin-3
  • sarafotoxin S6c
  • sex steroids

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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