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Effect of dexamethasone on endothelial nitric oxide synthase in experimental congenital diaphragmatic hernia
B O Okoye1, P D Losty, M J Fisher
1Department of Paediatric Surgery, Institute of Child Health, Alder Hey Children's Hospital, Liverpool.
Aims:
To study the effect of prenatal glucocorticoid treatment on endothelial nitric oxide synthase (eNOS) expression in rats with congenital diaphragmatic hernia (CDH).
Methods:
CDH was induced in fetal rats by the maternal administration of nitrofen on day 9.5 of gestation. Dexamethasone was administered on days 18.5 and 19.5 before delivery of the fetuses on days 20.5 and 21.5. Pulmonary eNOS protein expression was studied by western immunoblotting and immunohistochemistry.
Results:
On day 20.5, eNOS expression was significantly reduced in CDH pups compared with normal control rats. Dexamethasone treated CDH pups had eNOS concentrations equivalent to those of normal animals. By day 21.5, however, there was no detectable difference in eNOS expression between the experimental groups.
Conclusions:
eNOS is deficient in near term (day 20.5) CDH rats. Dexamethasone restores eNOS expression in these animals to that seen in normal rat lungs. At term, the precise role of eNOS in the pathophysiology of CDH remains uncertain.