Upregulation of eNOS in pregnant ovine uterine arteries by chronic hypoxia

We tested the hypothesis that chronic high-altitude (3,820 m) hypoxia durin g pregnancy was associated with the upregulation of endothelial nitric oxid e (NO) synthase (eNOS) protein and mRNA in ovine uterine artery endothelium and enhanced endothelium-dependent relaxation. In pregnant sheep, norepine phrine-induced dose-dependent contractions were increased by removal of the endothelium in both control and hypoxic uterine arteries. The increment wa s significantly higher in hypoxic tissues. The calcium ionophore A23187-ind uced relaxation of the uterine artery was significantly enhanced in hypoxic compared with control tissues. However, sodium nitroprusside- and 8-bromog uanosine 3',5'-cyclic monophosphate-induced relaxations were not changed. A ccordingly, chronic hypoxia significantly increased basal and A23187-induce d NO release. Chronic hypoxia increased eNOS protein and mRNA levels in the endothelium from uterine but not femoral or renal arteries. In nonpregnant animals, chronic hypoxia increased eNOS mRNA in uterine artery endothelium but had no effects on eNOS protein, NO release, or endothelium-dependent r elaxation. Chronic hypoxia selectively augments pregnancy-associated upregu lation of eNOS gene expression and endothelium-dependent relaxation of the uterine artery.