Although endothelin-1 (ET-1)-induced organ hypoperfusion following trauma-hemorrhage is improved by estrogen administration, it remains unclear whether estrogen receptor (ER) subtypes play any role in the attenuation of ET-1-induced vasoconstriction in any specific organ bed. To investigate this, isolated perfusion studies in heart, liver, small intestine, kidney and lung were carried out in sham, at the time of maximum bleedout (MBO, i.e., 5-cm midline incision, removal of 60% of circulating blood volume over 45 min to maintain mean BP of 40 mmHg), and two hr after trauma-hemorrhage and resuscitation (T-H/R). Organ-specific ET-1-induced vasoconstriction was evaluated and the effects of 17-estradiol (E2) and ER-specific agonist propylpyrazole triol (PPT; ER- agonist) and diarylpropionitrile (DPN; ER- agonist) were determined. ET-1 induced the greatest vasoconstriction in sham animals, with the strongest response in kidneys, followed by small intestine and liver. ET-1-induced responses were weakest in heart and lungs. ET-1-induced vasoconstriction was evident at the time of MBO but was significantly decreased at two hr after T-H/R. ER- plays an important role in cardiac performance as evidenced by improved heart performance (dP/dt) in the presence of DPN. DPN also induced a greater effect than PPT in reduction of ET-1-induced vasoconstriction in kidneys and lungs. In contrast, PPT attenuated ET-1-induced vasoconstriction in liver, while both DPN and PPT were equally effective in small intestine. The increased +dP/dt induced by E2, DPN, or PPT were evident at the time of MBO but were significantly decreased at two hr after T-H/R. These data indicate that the effects of ET-1 on vasoconstriction and the role of ER subtypes in estrogen-induced vasorelaxation are organ- and temporally-specific following trauma-hemorrhage.