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

Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030 We tested the hypothesis that endothelium-derived hyperpolarizing factor (EDHF) plays a less dominant role in the female cerebrovasculature. The contribution of EDHF to the ATP-mediated dilation was determined in middle cerebral arteries (MCAs) isolated from male and female rats. Four groups of rats were tested: intact male ( n = 12), intact female ( n = 13), estrogen-treated ovariectomized female ( n = 13), and vehicle-treated ovariectomized female ( n = 20) rats. Maximal dilation to ATP was similar in all groups. However, in the presence of N -nitro- L -arginine methyl ester ( L -NAME, 3 × 10 5 M) and indomethacin (10 5 M), the maximal dilation to ATP was significantly reduced in intact female (24 ± 9%) and estrogen-treated ovariectomized female (29 ± 9%) rats compared with intact male (95 ± 4%) and vehicle-treated ovariectomized female (96 ± 2%) rats. The ATP-mediated dilation in L -NAME- and indomethacin-treated MCAs isolated from male and ovariectomized female rats was inhibited by charybdotoxin (10 7 M), an inhibitor of large-conductance Ca 2+ -sensitive K + channels. We have defined EDHF as the L -NAME- and indomethacin-insensitive component of the ATP-mediated dilation. Our findings indicate that EDHF-mediated dilations are negligible in the female rat MCA; these dilations can be significantly enhanced after ovariectomy, suggesting that this effect is mediated by estrogen. gender; vascular