Sildenafil stimulates and dexamethasone inhibits pulmonary vascular development in congenital diaphragmatic hernia rat lungs

Background: A predictor of neonatal mortality in infants with congenital diaphragmatic hernia (CDH) is disrupted pulmonary vascular development, clinically expressed as pulmonary hypertension. Objective: To determine if prenatal corticosteroids and phosphodiesterase-5 (PDE-5) inhibitors have a beneficial effect on pulmonary vascular development in CDH lungs. Methods: We induced CDH in fetal rats by giving nitrofen. We then exposed them to dexamethasone or to sildenafil. We separated them into three groups: (1) DEX, 4 pregnant rats received dexamethasone at days E16, E18 and E20; (2) SILD, 4 pregnant rats received sildenafil and L-arginine between E14 and E22, and (3) placebo. We then analyzed the lung of each fetus with CDH at E22. We examined the number of arterioles and arteries, and their percent of medial wall thickness (%MWT). Results: We obtained 30 CDH-positive fetuses. We analyzed 3,560 arterioles and 211 arteries. SILD showed a significant increase in the number of arterioles, but no significant increase in the number of arteries. No change was noted in the arteriolar %MWT. In contrast, DEX showed significant decreases in the number of arterioles and arteries and a significant increase in %MWT. Conclusions: PDE-5 inhibitors may improve pulmonary arteriolar development in fetuses with CDH. In contrast, prenatal corticosteroids could have deleterious effects on arteriolar and arterial development in CDH lungs.