Ventilation causes pulmonary vascular dilation and modulates the NOS and VEGF pathway on newborn rats with CDH

• Published in: Journal of pediatric surgery Vol. 50; no. 5; pp. 842 - 848
• Main Authors: Gallindo, Rodrigo Melo, Gonçalves, Frances Lilian Lanhellas, Figueira, Rebeca Lopes, Pereira, Luís Antônio Violin Dias, Simões, Ana Leda Bertoncini, Schmidt, Augusto Frederico, Sbragia, Lourenço
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2015
• Subjects: Animals; Animals, Newborn; Congenital diaphragmatic hernia; Disease Models, Animal; Female; Hernia, Diaphragmatic - chemically induced; Hernia, Diaphragmatic - metabolism; Hernia, Diaphragmatic - physiopathology; Hernias, Diaphragmatic, Congenital - metabolism; Lung development; Nitric Oxide Synthase - metabolism; NOS; Pediatrics; Rats; Rats, Sprague-Dawley; Respiration, Artificial; Surgery; Vascular Endothelial Growth Factor A - metabolism; Vasodilation - physiology; VEGF; Ventilation; Ventilation; Congenital diaphragmatic hernia; Lung development; NOS; VEGF
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2014.12.005

Abstract Background/Purpose 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. Conclusion Ventilation caused pulmonary vasodilation and changed the expression of NOS and VEGF receptors.