Estrogen replacement effectively improves the accelerated intimal hyperplasia following balloon injury of carotid artery in the ovariectomized rats

Present experiments were designed to investigate the effects of ovariectomy (OVX) and estrogen replacement (ER) on neointimal formation after balloon injury of the rat carotid artery. Young adult female rats were divided into 3 groups of sham operation (control), ovariectomy, and ovariectomy plus estrogen replacement. Estrogen replacement was initiated by implanting a sustained release pellet containing water-soluble 17 beta-estradiol 1 week after the ovariectomy Carotid arteries were harvested 2 weeks after the balloon injury for determinations. The balloon injury caused intimal hyperplasia, which was accompanied by the impaired endothelium-dependent relaxation and cyclic GMP production, and accumulation of asymmetric dimethylarginine (ADMA) as an endogenous NOS inhibitor. Bilateral ovariectomy accelerated the intimal hyperplasia. The acceleration was accompanied by the enhanced impairment of NO production, attenuated reendothelialization, and enhanced accumulation of ADMA. The estrogen replacement improved the accelerated intimal hyperplasia with concomitant improvement of the impaired NO production and accumulated asymmetric dimethylarginine, and facilitated reendothelialization. These results suggests that the enhanced impairment of NO production, which possibly results from the accumulated asymmetric dimethylarginine and lack of reendothelialization, may contribute to the acceleration of intimal hyperplasia by ovariectomy and that estrogen replacement effectively improves the intimal hyperplasia by restoring the impaired NO production through reducing endogenous NOS inhibitor and facilitating reendothelialization.