A growing body of evidence indicates that
heme degradation products may counteract the deleterious consequences of
hypoxia and/or
ischemia-reperfusion injury. Because
heme oxygenase (HO)-1 induction after adverse circulatory conditions is known to be protective, and because females in the proestrus cycle (with high
estrogen) have better hepatic function and less hepatic damage than males after
trauma-
hemorrhage, we hypothesized that
estrogen administration in males after
trauma-
hemorrhage will upregulate HO activity and protect the organs against dysfunction and injury. To test this hypothesis, male Sprague-Dawley rats underwent 5-cm
laparotomy and
hemorrhagic shock (35-40 mmHg for 93 +/- 2 min), followed by
resuscitation with four times the shed blood volume in the form of Ringer
lactate. 17beta-Estradiol and/or the specific HO
enzyme inhibitor chromium mesoporphyrin (CrMP) were administered at the end of
resuscitation, and the animals were killed 24 h thereafter.
Trauma-
hemorrhage reduced cardiac output, myocardial contractility, and
serum albumin levels. Portal pressure and serum
alanine aminotransferase levels were markedly increased under those conditions. These parameters were significantly improved in the 17beta-estradiol-treated rats.
Estradiol treatment also induced increased HO-1
mRNA expression, HO-1
protein levels, and HO enzymatic activity in cardiac and hepatic tissue compared with vehicle-treated
trauma-
hemorrhage rats. Administration of the HO inhibitor CrMP prevented the
estradiol-induced attenuation of
shock-induced organ dysfunction and damage. Thus the salutary effects of
estradiol administration on organ function after
trauma-
hemorrhage are mediated in part via upregulation of HO-1 expression and activity.