Estradiol's effect on portal response to endothelin-1 after trauma-hemorrhage.
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 17beta-estradiol (E(2)) against hepatic damage following trauma-hemorrhage have been observed, it remains unknown whether E(2) directly improves hepatic circulation. We hypothesized that the salutary effects of E(2) are mediated, at least in part, by the attenuation of portal response to ET-1 following trauma-hemorrhage.


METHODS
Male adult Sprague-Dawley rats were randomly assigned to sham operation or trauma-hemorrhage with or without in vivo E(2) treatment. Trauma-hemorrhage included midline laparotomy and approximately 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 E(2) treatment group, 1 mg/kg of E(2) 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 E(2) treatment group. Furthermore, E(2) 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.
Yokoyama
Yukihiro
Y
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Toth
Balazs
B
Kitchens
William C
WC
Schwacha
Martin G
MG
Rue
Loring W
LW
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D001646:Bile / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D017082:Portal Pressure / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D012774:Shock, Traumatic / Q000503:physiopathology*
D019332:Endothelin-1; D004958:Estradiol; D007770:L-Lactate Dehydrogenase