Elevation of nitrate levels in pregnant ewes and their fetuses

OBJECTIVE: Nitric oxide is e potent vasodilator released by endothelial cells that may play an important role in modulating maternal and fetal vascular tone in normal pregnancy. The current study was designed to evaluate whether plasma or urine nitrite and nitrate (the metabolites of nitric oxide) concentrations are elevated in pregnant compared with those of nonpregnant sheep and whether the nitrate concentrations in the fetal circulation were increased in comparison with the maternal circulation. STUDY DESIGN: Eleven pregnant sheep and seven nonpregnant oophorectomized sheep were instrumented with catheters in the maternal and fetal femoral arteries and veins, uterine and umbilical veins, and amniotic cavity. Blood, urine, and amniotic fluid samples were collected for nitrate determination at least 5 days after surgery. After extraction nitrate was reduced to nitrite and quantitated with the Griess reagent. RESULTS: Arterial plasma nitrate concentrations in the pregnant sheep were significantly elevated compared with those of nonpregnant sheep (5.0 ± 0.9 vs 2.5 ± 0.6 μmol/L, p < 0.05). The urinary nitrate concentrations were also significantly increased in the pregnant sheep compared with those of nonpregnant sheep (89.9 ± 16.3 vs 23.1 ± 4.5 nmol/mg creatinine, p < 0.01). Fetal plasma nitrate concentrations were ninefold higher than the maternal nitrate concentrations (43.9 ± 7 vs 5.0 ± 0.9 μmol/L, p < 0.01), whereas amniotic fluid concentrations were extremely high (133.8 ± 13.8 μmol/L, n = 3). No venous-arterial differences were measurable across either the maternal or fetal sides of the placenta. CONCLUSION: Nitrate concentrations in pregnant sheep and their fetuses are increased. The increased nitrate concentrations in the maternal and fetal circulations may reflect the increased nitric oxide synthesis, which may in part mediate the cardiovascular adaptations to normal pregnancy and the low systemic and umbilical vascular resistance in the fetus.