SEXUALLY DIMORPHIC RESPONSE OF THE BALLOON-INJURED RAT CAROTID-ARTERYTO HORMONE-TREATMENT

Background Estrogen blunts the neointimal response to vascular injury in gonadectomized rats of both sexes; addition of a progestin blocks t he estrogen effect. This study tested, in intact rats of both sexes, w hether (1) exogenous estrogen has a vasoprotective effect in injured c arotid arteries, (2) progestin (medroxyprogesterone acetate, MPA) bloc ks the vasoprotective effect of estrogen, and (3) any observed sexual dimorphism in the responses to estrogen and/or MPA can be accounted fo r by differences in serum 17 beta-estradiol levels. Methods and Result s Intact male and female Sprague-Dawley rats were randomly divided int o four subgroups treated with either (1) 17 beta-estradiol, (2) MPA, ( 3) 17 beta-estradiol+MPA, or (4) vehicle and were subjected to balloon injury of the right common carotid artery. Two weeks later, rats were killed by an overdose of pentobarbital, and the carotid arteries were evaluated for myointimal thickening. Neither estradiol nor MPA altere d the neointimal response in males. In females, estradiol reduced and MPA enhanced the response, whereas addition of MPA to estradiol blocke d the vasoprotective effects of estrogen. Conclusions Intact male rats but not intact females are resistant to the vasoprotective effects of exogenous estrogen, despite attainment of physiological (for females) serum 17 beta-estradiol levels. MPA enhances the neointimal response in intact females, presumably by blocking the production and thus the vasoprotective effect of endogenous estrogen.