17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage

Zheng F. Ba, Ailing Lu, Tomoharu Shimizu, László Szalay, Martin G. Schwacha, Loring W. Rue, Kirby I. Bland, Irshad H. Chaudry

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22 Scopus citations

Abstract

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-β agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis.

Original languageEnglish (US)
Pages (from-to)H245-H250
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
StatePublished - Jan 1 2007

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Keywords

  • Aortic ring
  • Endothelium
  • Estrogen receptor
  • Nitric oxide

ASJC Scopus subject areas

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

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