title: Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats.
abstract: OBJECTIVE
  The use of dexamethasone (Dx) stimulates growth, fetal lung maturation and can improve pulmonary hypertension in congenital diaphragmatic hernia (CDH). Our aim was to evaluate the effect of Dx on the lung after fetal pulmonary ventilation in the CDH rat model.
  
  
  METHODS
  Some groups underwent prenatal treatment with dexamethasone (0.4 mg/kg) that was given at 18.5 gestational day (GD). Sprague-Dawley rat fetuses were divided into groups: control (C); ventilated control (CV); control exposed to dexamethasone (CDx); ventilated control exposed to dexamethasone (CVDx); congenital diaphragmatic hernia (CDH), ventilated CDH (CDHV), CDH exposed to dexamethasone (CDHDx) and ventilated CDH exposed to dexamethasone (CDHVDx). At 21.5 GD fetuses were delivered by C-section, weighed and ventilated for 30 min. We analyzed the lung morphometry by Masson's Trichrome stain, and VEGF, VEGFR1, VEGFR2 and NOS3 expression by immunohistochemistry.
  
  
  RESULTS
  All fetuses with CDH, with or without prenatal dexamethasone showed lung and body weight lower than control fetuses (p < 0.05). All groups that received dexamethasone showed a decrease in the medial muscular layer of arterioles, the internal diameter of the air spaces (Lma) and length of parenchymal transection/airspace ratio (p < 0.05). In the immunohistochemistry, VEGF decreased more in CDHDV group (p < 0.05). VEGFR1 showed no difference, whereas VEGFR2 decreased significantly in the CDHDV group (p < 0.05). NOS3 increased in the group CDHDV (p < 0.05).
  
  
  CONCLUSIONS
  The use of prenatal dexamethasone added to ventilation alters the VEGF and NO pathways.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery and Anatomy, Laboratory of Experimental Fetal Surgery "Michael R Harrison", Ribeirao Preto Medical School, University of Sao Paulo-USP, Av. Bandeirantes, 3900, Ribeirao Preto, SP, 14048-900, Brazil.
authors.forename: Frances Lilian Lanhellas
authors.initials: FL
authors.lastname: Gonçalves
authors.forename: Rebeca Lopes
authors.initials: RL
authors.lastname: Figueira
authors.forename: Ana Leda Bertoncini
authors.initials: AL
authors.lastname: Simões
authors.forename: Rodrigo Melo
authors.initials: RM
authors.lastname: Gallindo
authors.forename: Allan
authors.initials: A
authors.lastname: Coleman
authors.forename: José Luis
authors.initials: JL
authors.lastname: Peiró
authors.forename: Lourenço
authors.initials: L
authors.lastname: Sbragia
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D065630:Hernias, Diaphragmatic, Congenital / Q000196:embryology / Q000378:metabolism / Q000517:prevention & control*; D007150:Immunohistochemistry; D008168:Lung / Q000196:embryology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D005938:Glucocorticoids; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D003907:Dexamethasone