(Circulation. 2000;101:2342.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
Estrogen-Induced Vasoprotection Is Estrogen Receptor Dependent
Evidence From the Balloon-Injured Rat Carotid Artery Model
From thr Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine (S.B., T.M., J.D., Y.-F.C., S.O.), and Division of Transplantation, Department of Surgery (J.A.T.), University of Alabama at Birmingham, Ala.
Correspondence to Stephen Bakir, MD, 1047 ZRB, 703 South 19th St, Birmingham, AL 35294. E-mail sbakir{at}uab.edu
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 
or ß 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 17ß 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 protocol. Two weeks after injury, rats were killed, and the carotid arteries were evaluated for neointima formation using morphometric analysis. ICI 182,780 blunted the E2-related protective effect and increased neointima formation in injured carotid arteries of intact female rats in a dose-dependent fashion. ICI had no effect on neointima formation in OVX, but addition of ICI to E2 in OVX blocked the inhibitory effect of exogenous E2 on neointima formation.
Conclusions—These results indicate that the vasoprotective effect of E2 in the balloon-injured rat carotid artery model is mediated by ER.
Key Words: restenosis • hormones • carotid arteries • estrogen receptors
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