ESTROGEN RESTORES ENDOTHELIAL-CELL FUNCTION IN AN EXPERIMENTAL-MODEL OF VASCULAR INJURY

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 endoth elial cell function in balloon-injured rat carotid arteries. Methods a nd Results Ten-week-old male and female Sprague-Dawley rats with intac t gonads underwent balloon injury to the right common carotid artery. Female rats were randomized to receive either daily subcutaneous injec tions of 17 beta-estradiol (17 beta-E-2; 20 mu g.kg(-1).d(-1)) or vehi cle over the course of the study. Vessel morphology was assessed 2 wee ks after injury. Significant neointima formation was observed In vehic le-treated males, This response was blunted in vehicle-treated and 17 beta-E-2-supplemented females. Intima-to-media ratios were 1.28+/-0.23 (males), 0.72+/-0.07 (vehicle-treated females), and 0.49+/-0.07 (17 b eta-E-2-supplemented females). To test whether reductions in neointima l 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 we re precontracted with phenylephrine followed by cumulative administrat ion of acetylcholine, an endothelium-dependent vasodilator. Maximum re laxation to acetylcholine was 8.13+/-1.70% (males), 22.06+/-4.36% (veh icle-treated females), and 46.47+/-3.48% (17 beta-E-2-supplemented fem ales). The enhanced endothelium-dependent relaxation of rings from 17 beta-E-2-supplemented females correlated with reduced neointimal proli feration in this group. The concentration of nitric oxide metabolites in plasma correlated positively with plasma 17 beta-E-2 concentration. Conclusions These results suggest that estrogen protects against neoi ntimal injury in the balloon-injured rat, at least in part, by facilit ating the reendothelialization of the damaged vessel.