Role of estrogen in modulating EDHF-mediated dilations in the female rat middle cerebral artery

We tested the hypothesis that endothelium-derived hyperpolarizing factor (E DHF) plays a less dominant role in the female cerebrovasculature. The contr ibution of EDHF to the ATP- mediated dilation was determined in middle cere bral arteries (MCAs) isolated from male and female rats. Four groups of rat s were tested: intact male (n = 12), intact female (n = 13), estrogen-treat ed ovariectomized female (n = 13), and vehicle-treated ovariectomized femal e (n = 20) rats. Maximal dilation to ATP was similar in all groups. However , in the presence of N-omega-nitro-L-arginine methyl ester (L-NAME, 3 x 10 (-5) M) and indomethacin (10 (-5) M), the maximal dilation to ATP was signi ficantly reduced in intact female (24 +/- 9%) and estrogen-treated ovariect omized female (29 +/- 9%) rats compared with intact male (95 +/- 4%) and ve hicle-treated ovariectomized female (96 +/- 2%) rats. The ATP- mediated dil ation in L-NAME- and indomethacin-treated MCAs isolated from male and ovari ectomized female rats was inhibited by charybdotoxin (10(-7) M), an inhibit or of large-conductance Ca2+-sensitive K+ channels. We have defined EDHF as the L-NAME- and indomethacin-insensitive component of the ATP-mediated dil ation. Our findings indicate that EDHF-mediated dilations are negligible in the female rat MCA; these dilations can be significantly enhanced after ov ariectomy, suggesting that this effect is mediated by estrogen.