Mechanism of salutary effects of androstenediol on hepatic function after trauma-hemorrhage: Role of endothelial and inducible nitric oxide synthase

Tomoharu Shimizu, Laszlo Szalay, Mashkoor A. Choudhry, Martin G. Schwacha, Loring W. Rue, Kirby I. Bland, Irshad H. Chaudry

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Abstract

Recent studies have shown that administration of dehydroepiandrosterone (DHEA) after trauma-hemorrhage (T-H) improves cardiovascular and hepatic function in male animals. Although androstenediol, one of the DHEA metabolites, has been recently reported to produce salutary effects on cardiac function and splanchnic perfusion after T-H, it remains unknown whether androstenediol per se has any salutary effects on hepatic function under those conditions. To study this, male Sprague-Dawley rats underwent laparotomy and ∼90 min of hemorrhagic shock (35-40 mmHg), followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. Androstenediol (1 mg/kg body wt iv) was administered at the end of resuscitation, and the animals were killed 24 h later. T-H significantly reduced portal blood flow, bile production, and serum albumin levels. Portal pressure, serum alanine aminotransferase, hepatic nitrate/nitrite, inducible nitric oxide synthase (iNOS), and endothelin-1 markedly increased after T-H. The alterations in these parameters induced by T-H were significantly attenuated in rats treated with androstenediol. Endothelial NOS (eNOS) expression, which was not different between T-H and sham, was found to be significantly elevated in T-H androstenediol-treated rats. These data suggest that improvement in hepatic perfusion by androstenediol after T-H is likely due to a decrease in endothelin-1 and induction of eNOS. Moreover, the decrease in hepatic damage after androstenediol administration is likely related to liver iNOS downregulation. Thus androstenediol appears to be a novel and useful adjunct for restoring hepatic function in male animals after adverse circulatory conditions.

Original languageEnglish (US)
Pages (from-to)G244-G250
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume288
Issue number2 51-2
DOIs
Publication statusPublished - Feb 1 2005

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Keywords

  • 5-androstene-3β 17β-diol
  • Adiol
  • Hemorrhagic shock
  • Nitric oxide
  • Nitric oxide synthase-2

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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