Gender differences in coronary endotheliumdependent relaxations are mediated by metabolites of arachidonic acid

Experiments were designed to determine whether or not there are gender differences in expression of endothelium-dependent relaxations in porcine coronary arteries, and if so, to determine what endothelium-derived factors might contribute to these difference Coronary arteries from sexually mature, gonadally intact Yorkshire pigs of either sex were prepared for measurement of isometric force in organ chambers. In rings of right circumflex coronary arteries contracted with prostaglandin F_2α, endothelium-dependent relaxations to bradykinin and UK14.304 (α₂ agonist) but not A23187 (Ca²⁺ ionophore) were significantly greater in rings from female compared to male pigs. In rings without endothelium, relaxations to nitric oxide were the same between sexes. Endothelium-dependent relaxations to UK14.304 and A21387 were significantly increased by indomethacin in rings from male but not female pigs. The arginine analog L-NMMA decreased relaxations similarly in arteries from both male and female pigs Basal production of prostacyclin F_1α and thromboxane B₂ were higher in rings of arteries with endothelium from males. Collectively these data suggest gender differences in endothelium-dependent relaxations may not be mediated through direct effects on nitric oxide, but rather through differences in endothelium-dependent basal production of eicosanoids.