Estrogen-Induced Vasoprotection Is Estrogen Receptor Dependent

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Abstract
Background—Previous studies have shown that estrogen (E2) is vasoprotective in multiple animal models of vascular injury, including mice with homologous disruptions of either the α or β isoforms of the estrogen receptor (ER) gene, calling into question the ER dependency of the vasoprotective effect. This study used ICI 182,780, a nonselective ER antagonist, to test the hypothesis that the vasoprotective effect of E2 in the rat carotid injury model is ER mediated. Methods and Results—Intact female Sprague-Dawley rats were divided into 4 groups and treated with the nonselective ER antagonist ICI 182,780 (ICI; 0.5, 1.5, or 5 mg · kg−1 · d−1, subcutaneously [S.C.]) or vehicle, beginning before balloon injury of the right common carotid artery and continuing for 14 days afterward. Four groups of ovariectomized rats (OVX) were treated with 17β estradiol (E2) (20 μg · kg−1 · d−1, S.C.) alone or combined with ICI 5 mg · kg−1 · d−1, S.C.; with ICI 5 mg · kg−1 · d−1 alone; or with vehicle according to a similar pro...