Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage

Am J Physiol Regul Integr Comp Physiol. 2004 Aug;287(2):R386-90. doi: 10.1152/ajpregu.00214.2004. Epub 2004 Apr 29.


Recent studies have shown that dehydroepiandrosterone (DHEA) administration after trauma-hemorrhage (T-H) improves cardiovascular function and decreases cytokine production in male animals. Although androstenediol, one of the metabolites of DHEA, is reported to have estrogen-like activity, it remains unknown whether androstenediol per se has any salutary effects on cytokines and cardiovascular function after T-H. To examine this effect, male Sprague-Dawley rats underwent laparotomy and were bled to and maintained at a mean arterial blood pressure of 35-40 mmHg for approximately 90 min. The animals were resuscitated with four times the volume of maximal bleedout volume in the form of Ringer lactate. Androstenediol (1 mg/kg body wt i.v.) or vehicle was administered at the end of resuscitation. Twenty-four hours after resuscitation, cardiac function and organ blood flow were measured by using (85)Sr-microspheres. Circulating levels of nitrate/nitrite and IL-6 were also determined. Cardiovascular function and organ blood flow were significantly depressed after T-H. However, these parameters were restored by androstenediol treatment. The elevated plasma IL-6 levels after T-H were also lowered by androstenediol treatment. In contrast, plasma levels of nitrate/nitrite were the highest in the androstenediol-treated T-H animals. Because androstenediol administration after T-H decreases cytokine production and improves cardiovascular function, this agent appears to be a novel and useful adjunct for restoring the depressed cardiovascular function and for cytokine production in males after adverse circulatory conditions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anabolic Agents / pharmacology*
  • Androstenediol / pharmacology*
  • Animals
  • Cardiac Output / drug effects*
  • Interleukin-6 / blood
  • Laparotomy
  • Male
  • Nitrates / blood
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Nitrites / blood
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Hemorrhagic / drug therapy*
  • Splanchnic Circulation / drug effects*


  • Anabolic Agents
  • Interleukin-6
  • Nitrates
  • Nitrites
  • Nitric Oxide
  • Androstenediol
  • Nitric Oxide Synthase