Mechanisms Underlying Chronic Binge Alcohol Exposure‐Induced Uterine Artery Dysfunction in Pregnant Rat

Background A cardinal feature of fetal alcohol syndrome is growth restriction. Maternal uterine artery adaptations to pregnancy correlate with birthweight and survival. We hypothesized that gestational binge alcohol exposure impairs maternal uterine vascular function, affecting endothelial nitric oxide (NO)‐mediated vasodilation. Methods Pregnant rats grouped as pair‐fed control or binge alcohol exposed received a once‐daily, orogastric gavage of isocaloric maltose–dextrin or alcohol, respectively. On gestational day 20, primary uterine arteries were isolated, cannulated, and connected to a pressure transducer, and functional studies were conducted by dual‐chamber arteriography. Uterine arteries maintained at constant intramural pressure (90 mm Hg) were maximally constricted with thromboxane, and a dose–response for acetylcholine (Ach) was recorded. Results The alcohol group exhibited significantly impaired endothelium‐dependent, Ach‐induced uterine artery relaxation (↓∼30%). Subsequently, a dose–response was recorded following inhibition of endothelium‐derived hyperpolarizing factor (apamin and TRAM‐34) and prostacyclin (indomethacin). Ach‐induced relaxation in the pair‐fed control decreased by ~46%, and interestingly, relaxation in alcohol group further decreased by an additional ~48%, demonstrating that gestational binge alcohol impairs the NO system in the primary uterine artery. An endothelium‐independent sodium nitroprusside effect was not observed. Immunoblotting indicated that alcohol decreased the level of endothelial excitatory P‐Ser1177 endothelial NO synthase (eNOS) (p