O2--mediated impairment of coronary arterial relaxation is prevented by overnight treatment with 1 nM β-estradiol

We tested the hypothesis that the ability of coronary arteries to withstand functional damage from superoxide (02) is altered by exposure of the arteries to a physiological concentration of P-estradiol. Female porcine coronary arterial rings were incubated in an O-2-CO2 incubator, under normoxic conditions, at 37degreesC for 22-24 h. Arteries were then placed in baths containing a physiological salt solution at 37degreesC with 95% O-2-5% CO2 for isometric force recordings. In rings from 14 female pigs, vasorelaxation to A-23187 and diethylamine-NONOate (DEA-NONOate) was determined with and without prior 15-min exposure to 400 muM pyrogallol. Sensitivity (-logM ED50) and maximum relaxation to A-23187, but not DEA-NONOate, were significantly impaired by exposure to pyrogallol (pyrogallol treated: 7.39 +/- 0.09, 82 +/- 5%; control: 7.76 +/- 0.11, 99 +/- 1%, means +/- SE; P < 0.01 and P < 0.05, respectively). This effect was attenuated by concurrent exposure to equimolar ascorbate. Arterial rings from 12 separate female pigs were incubated for 22-24 h with or without 1 nM beta-estradiol before pyrogallol exposure. beta-Estradiol significantly enhanced arterial sensitivity to A-23187 and prevented pyrogallol impairment without affecting DEA-NONOate responses. Therefore, superoxide-mediated endothelial damage and impaired endothelium-dependent relaxation of coronary arteries are prevented by overnight exposure of the arteries to a physiological concentration of P-estradiol.