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

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Abstract
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 ω-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 Ca2+-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.

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