Abstract 380 Developmental Pharmacology: Drug Effects on Neonatal Angiogenesis and Vascular Function Platform, Monday, 5/3

Antenatal administration of glucocorticoids has been shown to improve postnatal lung function after preterm birth in the ovine fetus. Mechanisms of steroid-induced lung maturation include increased surfactant production and altered parenchymal lung structure. Whether steroid treatment also affects lung vascular function is unclear. Since nitric oxide (NO) contributes to the fall in pulmonary vascular resistance at birth, we hypothesized that the improvement in postnatal lung function of preterm lambs after treatment with prenatal glucocorticoids may be in part due to an increase in endothelial NO synthase (eNOS) activity. To determine whether glucocorticoid treatment increases lung eNOS expression, we measured eNOS protein content by western blot in distal lung homogenates and immunostaining in lungs from ovine fetuses delivered at preterm and term gestation after prenatal administration of glucocorticoids. Multiple treatment protocols were followed in which ewes were treated with intramuscular betamethasone (0.5 mg/kg) at single or multiple doses at weekly intervals and then delivered at 125, 135, or 145 days gestation. All treatment groups were compared with saline-treated controls. Sheep were sacrificed after delivery and lung tissue frozen until the time of assay. Immunostaining of lung tissues showed staining predominantly for vascular endothelium in all sized vessels. Pattern of staining was not altered by treatment with antenatal glucocorticoids. Western blot analysis of whole lung homogenates demonstrated a 5-fold increase in eNOS protein content in lambs treated with repetitive doses of glucocorticoids after delivery at term (145 days); p<0.05. In comparison with control animals, there were no differences in lung eNOS content from lambs treated with single or multiple doses when delivery occurred at preterm ages (125 and 135 days). We conclude that maternal treatment with glucocorticoids increases lung eNOS content after multiple doses and delivery at term gestation. We speculate that antenatal glucocorticoids can upregulate eNOS content, but that the response is critically dependent upon the timing of steroid treatment. The mechanism by which maternal glucocorticoid treatment can increase eNOS expression and its physiologic implications are uncertain.