Long-term high-altitude hypoxia increases plasma nitrate levels in pregnant ewes and their fetuses

The study was designed to determine whether moderate chronic hypoxia changes plasma nitrate concentrations in nonpregnant and pregnant, near-term ewes and their fetuses.

Pregnant ewes were put into either a normoxic control group or a chronically hypoxic group maintained at high altitude (3820 m, PaO 2 60 mm Hg) from day 30 of gestation. On day 140 blood samples were collected from the maternal jugular vein and from the fetal umbilical artery and vein. Blood samples were also obtained from normoxic nonpregnant adult ewes and nonpregnant adult ewes exposed to high-altitude hypoxia for 110 days. Plasma nitrate concentrations were determined through chemiluminescence assay.

Within normoxic groups plasma nitrate concentrations of pregnant, near-term ewes were significantly elevated compared with those of nonpregnant ewes (17.4 +/- 0.3 vs 6.8 +/- 0.4 micromol/L, P <.0001). Fetal umbilical arterial and venous plasma nitrate concentrations did not differ from each other in the normoxic group (44.7 +/- 4.2 and 44.0 +/- 4.3 micromol/L, respectively) but were significantly higher than those of their mothers (P <.0001). Compared with normoxic groups, pregnant ewes with chronic hypoxia showed significantly increased plasma nitrate concentrations (30.9 +/- 1.8 micromol/L, P <.001), as did their fetuses (arterial 146.1 +/- 14.7 micromol/L, venous 154.5 +/- 14.6 micromol/L, P <.0001), but nonpregnant ewes with chronic hypoxia did not (7.5 +/- 0.3 micromol/L, P >.05).

We conclude that (1) production of endogenous nitric oxide is increased by pregnancy in sheep and is higher in the fetus than in the mother, and (2) moderate chronic hypoxia selectively augments nitric oxide production in the pregnant ewe's circulation and, even more profoundly, in the fetal lamb's circulation.