Long term effects of prenatal hypoxia on endothelium‐dependent relaxation responses in pulmonary vessels of adult sheep

We reported that chronically hypoxic fetuses (pregnant ewes kept at 3820 m high altitude from 35 to 145 d gestation; controls at sea level) exhibited altered pulmonary vascular reactivity (AJP: Lung, Epub, 2006). However, the long term effects of prenatal hypoxia on the pulmonary vasculature are not known. Therefore, we studied isolated intrapulmonary arteries and veins of adult sheep that were hypoxic as fetuses but were raised at sea level until 14 months of age (prenatal hypoxia) and adult sheep raised at sea level (control). In arteries and veins constricted with endothelin‐1, acetylcholine and bradykinin elicited attenuated relaxation, in prenatal hypoxia compared to controls (n=4–5, each group). There were no differences in relaxation to DETA‐NONOate (an NO donor) between vessels from prenatal hypoxia and control groups, after inhibition of endothelial nitric oxide synthase (eNOS). eNOS protein expression was unchanged but eNOS activity was significantly decreased in arteries from prenatal hypoxia group. However, both protein expression and activity of eNOS were significantly decreased in veins from prenatal hypoxia group compared to controls (n=7–8, each group). Our results show that prenatal hypoxia results in persistent abnormalities in relaxation responses of pulmonary arteries and veins in adult sheep and that this is due to decreased activity and/or abundance of eNOS. Grants 059435, 075187.