Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats

Author(s)

Lanhellas Goncalves, Frances Lilian ^[1] ; Figueira, Rebeca Lopes ^[1] ; Simoes, Ana Leda Bertoncini ^[1] ; Gallindo, Rodrigo Melo ^[1] ; Coleman, Allan ^[2] ; Peiro, Jose Luis ^[2] ; Sbragia, Lourenco ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Lab Expt Fetal Surg Michael R Harrison, Div Pediat Surg, Dept Surg & Anat, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH - USA

• Document type: Journal article
• Source: PEDIATRIC SURGERY INTERNATIONAL; v. 30, n. 12, p. 1207-1215, DEC 2014.
• Web of Science Citations: 5

Abstract

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. 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. 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). The use of prenatal dexamethasone added to ventilation alters the VEGF and NO pathways. (AU)

• FAPESP's process: 11/12587-0 - Evaluation in vivo of the effect of corticosteroids and ventilation in oxide nitric pathway on the expression of VEGF and its pulmonary receptors after fetal tracheal occlusion in the congenital diaphragmatic hernia in rats
• Grantee: Frances Lilian Lanhellas Gonçalves
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/00794-1 - Assessment of nitric oxide (NO) in vivo after fetal tracheal occlusion on the expression of VEGF receptors in pulmonary congenital diaphragmatic hernia induced by Nitrofen
• Grantee: Lourenço Sbragia Neto
• Support Opportunities: Regular Research Grants