O2(-)-mediated impairment of coronary arterial relaxation is prevented by overnight treatment with 1 nM beta-estradiol.
We tested the hypothesis that the ability of coronary arteries to withstand functional damage from superoxide (O(2)(-)) is altered by exposure of the arteries to a physiological concentration of beta-estradiol. Female porcine coronary arterial rings were incubated in an O(2)-CO(2) incubator, under normoxic conditions, at 37 degrees C for 22-24 h. Arteries were then placed in baths containing a physiological salt solution at 37 degrees C with 95% O(2)-5% CO(2) 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 microM pyrogallol. Sensitivity (-logM ED(50)) 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 beta-estradiol.
Bell
David R
DR
Department of Cellular and Integrative Physiology, Indiana University, School of Medicine, Fort Wayne, Indiana 46805-1499, USA. bell@ipfw.edu
Gochenaur
Kristen E
KE
Hecht
Jennifer
J
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology*; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D010100:Oxygen / Q000494:pharmacology*; D011748:Pyrogallol / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine
D006834:Hydrazines; D007476:Ionophores; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D011748:Pyrogallol; D000001:Calcimycin; D004958:Estradiol; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D010100:Oxygen