Antenatal dexamethasone enhances endothelin receptorB expression in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats

Background/Purpose: The hypoplastic lung and persistent pulmonary hypertension (PPH) are the principle causes of high mortality and morbility in infants with congenital diaphragumatic hernia (CDH). Endothelin-1 (ET-1), which is produced by Vascular endothelial cells and some leukocytes, plays a key role in modulating pulmonary Vascular tone in PPH. Two different receptors (ETA and ETB) for ET-1 have been characterized. Binding of ET-1 to ETA, which is present on smooth muscle cells in fetal lung, results in vasoconstriction. However, binding of ET-1 to ETB, which is present on endothelial cells results in vasodilation mediated by endogenous nitric oxide. Antenatal glucocorticoid therapy has been shown to prevent abnormal pulmonary arterial structural changes in animal model with CDH. The aim of this study was to investigate the effect of antenatal glucocorticoid administration on ET-1 system in nitrofen-induced CDH hypoplastic lung in rats. Methods: A CDH model was induced in pregnant rats after administration of nitrofen on day 9.5 of gestation. Dexamethazone (Dex) was given intraperitoneally on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. Rat ET-1 protein expression was measured in solubilized lung tissue extracts, by sandwich type enzyme-linked immunosorbent assay (ELISA) analysis. Reverse transcription polymerase chain reaction was performed to evaluate the relative amount of ET-1, ETA, and ETB mRNA expression. Results: The ET-1 protein and mRNA expression of ET-1 and both receptors were increased significantly in CDH lung compared with controls. Although there was no significant difference in ETA mRNA expression between CDH lung with Dex treatment and without Dex treatment, ETB mRNA expression was elevated significantly in CDH lung with Dex treatment compared with CDH lung without Dex treatment. Conclusion: These findings suggest that antenatal glucocorticoid therapy may modulate pulmonary Vascular tone in CDH hypoplastic lung by selectively upregulating local expression of ETB. J Pediatr Surg 35:203-207. Copyright (C) 2000 by W.B. Saunders Company.