Role of estrogen in modulating EDHF-mediated dilations in the female rat middle cerebral artery.
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(omega)-nitro-L-arginine methyl ester (L-NAME, 3 x 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.
Golding
E M
EM
Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030, USA. egolding@bcm.tmc.du
Kepler
T E
TE
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001685:Biological Factors / Q000378:metabolism* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010052:Ovariectomy; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
C105785:1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D006834:Hydrazines; D051036:Large-Conductance Calcium-Activated Potassium Channels; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; C067410:endothelium-dependent hyperpolarization factor; D000255:Adenosine Triphosphate; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin