Estradiol's effect on portal response to endothelin-1 after trauma-hemorrhage

Yukihiro Yokoyama, Balazs Toth, William C. Kitchens, Martin G. Schwacha, Loring W. Rue, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background The fine balance between vasoconstrictors and vasodilators maintains portal circulation. Studies have shown that portal response to endothelin-1 (ET-1), a potent vasoconstrictor, is enhanced following hemorrhagic-shock, which subsequently leads to the impaired hepatic circulation and hepatic damage. Although protective effects of 17β-estradiol (E 2) against hepatic damage following trauma-hemorrhage have been observed, it remains unknown whether E2 directly improves hepatic circulation. We hypothesized that the salutary effects of E2 are mediated, at least in part, by the attenuation of portal response to ET-1 following trauma-hemorrhage. Materials and methods Male adult Sprague-Dawley rats were randomly assigned to sham operation or trauma-hemorrhage with or without in vivo E2 treatment. Trauma-hemorrhage included midline laparotomy and ∼90 min of hemorrhagic shock (35 mmHg), then resuscitation with four times the shed blood volume with Ringer's lactate solution over 60 min. For the E2 treatment group, 1 mg/kg of E2 was added to the Ringer's lactate solution. At 5 h after the end of resuscitation, the liver was isolated and perfused in vitro to measure portal pressure responses to exogenous ET-1 (60 pmol in 150 ml perfusate, bolus) with or without E 2 (1,500 pg/ml). Results Peak portal pressure after the administration of ET-1 was significantly higher in vehicle-treated trauma-hemorrhage group compared with the sham group. This effect was significantly attenuated in the E2 treatment group. Furthermore, E2 treatment restored bile production and prevented hepatic damage following trauma-hemorrhage. Conclusions The beneficial effects of estradiol observed following trauma-hemorrhage, at least partly, are caused by the attenuation of portal pressure response to increased ET-1.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalJournal of Surgical Research
Volume121
Issue number1
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

Keywords

  • bile flow
  • hepatic damage
  • isolated liver perfusion
  • portal venous pressure

ASJC Scopus subject areas

  • Surgery

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