Dietary l-arginine prevents fetal growth restriction in rats

Objective: Alterations in maternal plasma arginine concentration accompany normal pregnancy. Nitric oxide is synthesized from l-arginine and influences fetal growth. We hypothesized that l-arginine would influence fetal growth and hypoxia-induced uricemia in a maternal hypoxia-induced fetal growth restriction model. Study Design: Fetal growth on day 21 of gestation was assessed in timed pregnant Wistar rats with or without exposure to maternal hypobaric hypoxia. Animals exposed to hypoxia received either no supplement or supplementation of drinking water with 0.2% l-arginine, 2% l-arginine, or 2% glycine. On day 21 of gestation, fetuses were delivered by hysterotomy and fetal and placental weights were obtained. Maternal and fetal plasma were assayed for uric acid as an index of tissue hypoxia. Xanthine oxidase and xanthine dehydrogenase, precursors of uric acid and reactive oxygen species, were assayed in maternal tissue. Results were analyzed by analysis of variance with correction for multiple comparisons. Results: Exposure of rats on normal diets to hypoxia resulted in a 30% reduction in fetal weights. l-Arginine, 2% or 0.2%, prevented the reduction in fetal weight (p<0.0001). Isocaloric and isonitrogenous supplementation with glycine did not influence hypoxia-induced fetal growth restriction. Conclusion: l-Arginine, but not glycine, ameliorates maternal hypoxia-induced fetal growth restriction in the rat.