Estrogen restores endothelial cell function in an experimental model of vascular injury

被引:83
作者
White, CR
Shelton, J
Chen, SJ
DarleyUsmar, V
Allen, L
Nabors, C
Sanders, PW
Chen, YF
Oparil, S
机构
[1] UNIV ALABAMA,DEPT VASC BIOL,BIRMINGHAM,AL 35294
[2] UNIV ALABAMA,HYPERTENS PROGRAM,BIRMINGHAM,AL 35294
[3] DEPT VET AFFAIRS MED CTR,DEPT PATHOL,BIRMINGHAM,AL
[4] DEPT VET AFFAIRS MED CTR,DEPT PHYSIOL,BIRMINGHAM,AL
[5] DEPT VET AFFAIRS MED CTR,DEPT NEPHROL,BIRMINGHAM,AL
[6] CTR FREE RAD BIOL,BIRMINGHAM,AL
关键词
hormones; balloon; vasculature;
D O I
10.1161/01.CIR.96.5.1624
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 17 beta-estradiol (17 beta-E-2; 20 mu g.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 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 beta-E-2-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% (17 beta-E-2-supplemented females). The enhanced endothelium-dependent relaxation of rings from 17 beta-E-2-supplemented females correlated with reduced neointimal proliferation 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 neointimal injury in the balloon-injured rat, at least in part, by facilitating the reendothelialization of the damaged vessel.
引用
收藏
页码:1624 / 1630
页数:7
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