Antenatal steroid and tracheal occlusion restore vascular endothelial growth factor receptors in congenital diaphragmatic hernia rat model.
OBJECTIVE
Investigate the effects of antenatal steroids and tracheal occlusion on pulmonary expression of vascular endothelial growth factor receptors in rats with nitrofen-induced congenital diaphragmatic hernia.


METHODS
Fetuses were exposed to nitrofen at embryonic day 9.5. Subgroups received dexamethasone or were operated on for tracheal occlusion, or received combined treatment. Morphologic variables were recorded. To analyze vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, we performed Western blotting and immunohistochemistry. Morphologic variables were analyzed by analysis of variance and immunohistochemistry by Kruskal-Wallis test.


RESULTS
Congenital diaphragmatic hernia decreased body weight, total lung weight, and lung-to-body weight ratio. Tracheal occlusion increased total lung weight and lung-to-body weight ratio (P < .05). Fetuses with congenital diaphragmatic hernia had reduced vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, whereas steroids and tracheal occlusion increased their expression. Combined treatment increased expression of receptors, but had no additive effect.


CONCLUSIONS
Vascular endothelial growth factor signaling disruption may be associated with pulmonary hypertension in congenital diaphragmatic hernia. Tracheal occlusion and steroids provide a pathway for restoring expression of vascular endothelial growth factor receptors.
Division of Pediatric Surgery, Department of Surgery, School of Medical Sciences, University of Campinas, UNICAMP, Campinas, SP, Brazil.
Augusto F
AF
Schmidt
Frances L L
FL
Gonçalves
Azize C C
AC
Nassr
Luis A V D
LA
Pereira
Diana
D
Farmer
Lourenço
L
Sbragia
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000196:embryology / Q000378:metabolism*; D065630:Hernias, Diaphragmatic, Congenital; D007150:Immunohistochemistry; D018811:Maternal Exposure; D010647:Phenyl Ethers; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013256:Steroids / Q000494:pharmacology*; D014135:Tracheal Stenosis / Q000378:metabolism / Q000503:physiopathology*
D010647:Phenyl Ethers; D013256:Steroids; D040262:Receptors, Vascular Endothelial Growth Factor; C007350:nitrofen