title: Sildenafil stimulates and dexamethasone inhibits pulmonary vascular development in congenital diaphragmatic hernia rat lungs.
abstract: 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.
authors.affiliation: Division of Neonatology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Javier
authors.initials: J
authors.lastname: Kattan
authors.forename: Carlos
authors.initials: C
authors.lastname: Céspedes
authors.forename: Alvaro
authors.initials: A
authors.lastname: González
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Vio
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D065630:Hernias, Diaphragmatic, Congenital / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D007150:Immunohistochemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
chemical_list: D000199:Actins; D003907:Dexamethasone; D005938:Glucocorticoids; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011687:Purines; D000068677:Sildenafil Citrate; D013449:Sulfonamides; C498862:Acta2 protein, rat