Differential expression of placental and vascular endothelial nitric oxide synthase in an ovine model of fetal growth restriction

Objective The objective of the study was to evaluate endothelial nitric oxide synthase concentration in the placenta, uterine, and umbilical vessels near term in an ovine model of intrauterine growth restriction induced by hyperthermia beginning in early gestation. Study design Four pregnant ewes were exposed to hyperthermia conditions for 80 days beginning at 35 days gestation to induce intrauterine growth restriction. Four ewes were kept in ambient conditions as controls. Umbilical artery Doppler systolic to diastolic ratios were calculated. At 128 days gestation, fetal catheters were placed for aortic blood pressure measurements and blood gas determination. At 132 days gestation, fetal mean systemic blood pressure and gases were determined. Sheep placentomes, umbilical artery and vein, and uterine artery were assessed for endothelial nitric oxide synthase concentration and immunolocalization. Results Compared with control pregnancies, the intrauterine growth restriction pregnancies showed: (1) reduced fetal and placental weights ( P ≤ .01); (2) elevated systemic blood pressure (41 ± 1.53 mm Hg versus 44.3 ± 1.71 mm Hg; P ≤ .05) and systolic to diastolic ratios (3.0 ± 0.34 versus 3.8 ± 0.18; P ≤ .01); (3) reduced fetal O 2 saturation (52.2 ± 7.03% versus 33.05 ± 10.98%; P ≤ .008); and (4) decreased endothelial nitric oxide synthase protein concentration in the umbilical artery (2.7-fold; P ≤ .01) and a trend for a decrease in the uterine artery (1.4-fold; P ≤ .1). Conclusion We conclude that placental endothelial nitric oxide synthase protein concentration is increased near term in our ovine model of intrauterine growth restriction, and that this increase may be secondary to hypoxia.