STEREOISOMER-SPECIFIC INHIBITION OF SUPEROXIDE ANION-INDUCED RAT AORTIC SMOOTH-MUSCLE CELL-PROLIFERATION BY 17-BETA-ESTRADIOL IS ESTROGEN-RECEPTOR DEPENDENT

An in vitro xanthine/xanthine oxidase reaction system was used to gene rate superoxide anions that significantly stimulated tritiated [H-3]th ymidine incorporation into endothelium-removed (denuded) male rat aort ic explants. Tritiated thymidine uptake was used as an index of vascul ar smooth-muscle cell (VSMC) proliferation. Superoxide dismutase (SOD) significantly attenuated the oxygen free radical-induced proliferativ e response of these cells. 17 beta-estradiol (17 beta-E) significantly inhibited superoxide anion-induced VSMC proliferation. in contrast, t he growth-modifying effects of 17 beta-E were not mimicked by 17 alpha -estradiol (17 alpha-E), progesterone, or testosterone. The pure estro gen receptor (ER) antagonist, ICI 164,384, reversed the growth-inhibit ory effect of 17 beta-E. 17 beta-Estradiol failed directly to reduce i n vitro superoxide anion production or to modify xanthine oxidase acti vity. Therefore, these data indicate that 17 beta-E, through an ER-dep endent mechanism, specifically and significantly inhibited superoxide anion-mediated SMC proliferation in denuded rat aortic explants.