title: Ventilation causes pulmonary vascular dilation and modulates the NOS and VEGF pathway on newborn rats with CDH.
abstract: OBJECTIVE
  Congenital diaphragmatic hernia (CDH) is a defect that presents high mortality because of pulmonary hypoplasia and hypertension. Mechanical ventilation changes signaling pathways, such as nitric oxide and VEGF in the pulmonary arterioles. We investigated the production of NOS2 and NOS3 and expression of VEGF and its receptors after ventilation in rat fetuses with CDH.
  
  
  METHODS
  CDH was induced by Nitrofen. The fetuses were divided into 6 groups: 1) control (C); 2) control ventilated (CV); 3) exposed to nitrofen (N-); 4) exposed to nitrofen ventilated (N-V), 5) CDH and 6) CDH ventilated (CDHV). Fetuses were harvested and ventilated. We assessed body weight (BW), total lung weight (TLW), TLW/BW ratio, the median pulmonary arteriolar wall thickness (MWT). We analyzed the expression of NOS2, NOS3, VEGF and its receptors by immunohistochemistry and Western blotting.
  
  
  RESULTS
  BW, TLW, and TLW/BW ratio were greater on C than on N- and CDH (p<0.05). The MWT was higher in CDH than in CDHV (p<0.001). CDHV showed increased expression of NOS3 (p<0.05) and VEGFR1 (p<0.05), but decreased expression of NOS2 (p<0.05) and VEGFR2 (p<0.001) compared to CDH.
  
  
  CONCLUSIONS
  Ventilation caused pulmonary vasodilation and changed the expression of NOS and VEGF receptors.
authors.affiliation: Laboratory of Experimental Fetal Surgery, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Rodrigo Melo
authors.initials: RM
authors.lastname: Gallindo
authors.affiliation: Laboratory of Experimental Fetal Surgery, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Frances Lilian Lanhellas
authors.initials: FL
authors.lastname: Gonçalves
authors.affiliation: Laboratory of Experimental Fetal Surgery, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Rebeca Lopes
authors.initials: RL
authors.lastname: Figueira
authors.affiliation: Department of Histology and Embryology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Luís Antônio Violin Dias
authors.initials: LA
authors.lastname: Pereira
authors.affiliation: Laboratory of Experimental Fetal Surgery, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Ana Leda Bertoncini
authors.initials: AL
authors.lastname: Simões
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Augusto Frederico
authors.initials: AF
authors.lastname: Schmidt
authors.affiliation: Laboratory of Experimental Fetal Surgery, Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. Electronic address: sbragia@fmrp.usp.br.
authors.forename: Lourenço
authors.initials: L
authors.lastname: Sbragia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D065630:Hernias, Diaphragmatic, Congenital / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D019001:Nitric Oxide Synthase
keywords: Congenital diaphragmatic hernia; Lung development; NOS; VEGF; Ventilation