(Circulation. 1997;96:1624-1630.)
© 1997 American Heart Association, Inc.
Articles |
Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury
From the University of Alabama at Birmingham, Departments of Medicine, Vascular Biology, and Hypertension Program (C.R.W., J.S., S.-J.C., L.A., P.W.S., Y.-F.C., S.O.), Pathology (V.D.-U.), Physiology (S.O.), and Nephrology (C.N., P.W.S.); the Department of Veterans Affairs Medical Center (P.W.S.); and the Center for Free Radical Biology (C.R.W., V.D.-U.), Birmingham, Ala.
Correspondence to C. Roger White, PhD, Departments of Medicine, Vascular Biology, and Hypertension Program, 1046 Zeigler Research Bldg, 703 S 19th St, Birmingham, AL 35294-0007. E-mail card029{at}uabdpo.dpo.uab.edu
Background It has been suggested that reendothelialization of damaged blood vessels protects against the vascular injury response. The goal of the present study was to determine whether estrogen restores endothelial cell function in balloon-injured rat carotid arteries.
Methods and Results Ten-week-old male and female Sprague-Dawley rats with intact gonads underwent balloon injury to the right common carotid artery. Female rats were randomized to receive either daily subcutaneous injections of 17ß-estradiol (17ß-E2; 20 µg · kg-1 · d-1) or vehicle over the course of the study. Vessel morphology was assessed 2 weeks after injury. Significant neointima formation was observed in vehicle-treated males. This response was blunted in vehicle-treated and 17ß-E2–supplemented females. Intima-to-media ratios were 1.28±0.23 (males), 0.72±0.07 (vehicle-treated females), and 0.49±0.07 (17ß-E2–supplemented females). To test whether reductions in neointimal lesion formation were related to the functional reendothelialization of the damaged vessel, endothelium-dependent relaxation was tested in isolated ring segments from the three experimental groups. Vessels were precontracted with phenylephrine followed by cumulative administration of acetylcholine, an endothelium-dependent vasodilator. Maximum relaxation to acetylcholine was 8.13±1.70% (males), 22.06±4.36% (vehicle-treated females), and 46.47±3.48% (17ß-E2–supplemented females). The enhanced endothelium-dependent relaxation of rings from 17ß-E2–supplemented females correlated with reduced neointimal proliferation in this group. The concentration of nitric oxide metabolites in plasma correlated positively with plasma 17ß-E2 concentration.
Conclusions These results suggest that estrogen protects against neointimal injury in the balloon-injured rat, at least in part, by facilitating the reendothelialization of the damaged vessel.
Key Words: hormones • balloon • vasculature
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