Systematic analysis of the salutary effect of estrogen on cardiac performance after trauma-hemorrhage.
Although 17beta-estradiol (estrogen) and estrogen receptor (ER) agonist administration after trauma-hemorrhage improves cardiac function, it remains unknown what the optimal estrogen or ER agonist dosage is to elicit this beneficial effect. To study this, the dose-dependent effects of estrogen, propylpyrazole triol (ER-alpha agonist), and diarylpropionitrile (DPN; ER-beta agonist) on heart performance (+dP/dt) were determined in sham rats and in experimental animals at the time of maximal bleedout (MBO) or at 2 h after trauma-hemorrhage. The results showed that estrogen and DPN induced dose-dependent increases in the maximal rate of left ventricular pressure increase (+dP/dt) in all groups, whereas propylpyrazole triol was ineffective at all doses. The maximal dose and the 50% effective dose of DPN were approximately 100-fold lower than those of estrogen. The half-life of estrogen in plasma was approximately 25 min in sham and MBO groups. A positive correlation between the estrogen-induced increase in +dP/dt and survival in MBO rats were observed. These results collectively suggest that the salutary effects of estrogen on cardiac performance are dose-dependent and mediated via ER-beta.
Ba
Zheng F
ZF
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
Hsu
Jun-Te
JT
Chen
Jianguo
J
Kan
Wen-Hong
WH
Schwacha
Martin G
MG
Chaudry
Irshad H
IH
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000819:agonists; D004967:Estrogens / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006470:Hemorrhage / Q000503:physiopathology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047629:Estrogen Receptor beta; D004967:Estrogens; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol