title: Tracheal occlusion and ventilation changes the nitric oxide pathway in congenital diaphragmatic hernia model.
abstract: Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension. Tracheal occlusion (TO) stimulates fetal lung growth and maturation and reverse vascular changes responsible for pulmonary hypertension, which are related to mechanisms involving nitric oxide (NO) in CDH. We aim to evaluate the effect of TO and ventilation on NO pathways.
  
  
  
  Eight groups were created: (1) control; (2) control ventilated (CV); (3) CDH (CDH); (4) CDH ventilated (CDHV); (5) TO control; (6) TO ventilated; (7) TO + CDH; and (8) TO + CDH ventilated (CDHTOV). Fetuses were weighed, and volume ventilated for 30 min after harvested. Total lung weight and the ratio of total lung weight to body weight, thickness of the middle layer of the pulmonary arteriole, and the air space diameter were measured. The NO synthase inducible and NO synthase inducible were performed by immunohistochemistry and Western blotting.
  
  
  
  The total lung weight and the ratio of total lung weight to body weight decreased in animals with nitrofen and also after ventilation for all groups (P < 0.05). The thickness of the middle layer of the pulmonary arteriole decreased in all groups with TO when compared with controls (P < 0.001). The air space diameter decreased after ventilation in the CDHTOV compared to the TO + nitrofen-induced CDH (P < 0.001). Compared to nonventilated cohorts, NO synthase inducible increased in CV and TO ventilated (P < 0.001) and decreased in CDHV and CDHTOV (P < 0.001). NO synthase inducible increased in CV and CDHV (P < 0.001) and decreased in the TO control and CDHTOV (P < 0.001).
  
  
  
  TO and ventilation alter the NO pathway with possible implications in reducing the pulmonary hypertension in CDH.
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: 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: Ana Leda Bertoncini
authors.initials: AL
authors.lastname: Simões
authors.affiliation: Pediatric General and Thoracic Surgery, Division of Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Alan
authors.initials: A
authors.lastname: Coleman
authors.affiliation: Pediatric General and Thoracic Surgery, Division of Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Peiró
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; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D046128:Fetal Therapies / Q000379:methods; D065630:Hernias, Diaphragmatic, Congenital / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007150:Immunohistochemistry; D008168:Lung / Q000196:embryology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D060205:Therapeutic Occlusion
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat
keywords: Congenital diaphragmatic hernia; Nitric oxide; Nitric oxide synthase; Pulmonary ventilation; Tracheal occlusion