Cardiac gene expression and synthesis of atrial natriuretic peptide in the nitrofen model of congenital diaphragmatic hernia in rats: effect of prenatal dexamethazone treatment.
OBJECTIVE
The aim of this study was to determine the gene and protein levels of atrial natriuretic peptide (ANP) in the heart of nitrofen-induced congenital diaphragmatic hernia (CDH) in rats and to evaluate the effect of antenatal dexamethazone (Dex) treatment.


METHODS
CDH model was induced in pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation (term, day 22). Dexamethazone (Dex, 0.25 mg/kg) was given by intraperitoneal injection on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. The fetuses were divided into 3 groups: group I, control (n = 10); group II, nitrofen-induced CDH (n = 10); group III, nitrofen-induced CDH with antenatal Dex treatment (n = 10). ANP protein was measured using enzyme-linked immunosorbent assay (ELISA) technique. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of atrial natriuretic peptide (ANP) mRNA expression.


RESULTS
There was a significant reduction in ANP mRNA (P <.05) and protein (P <.01) levels in heart of group II (CDH) compared with group I. Antenatal Dex treatment significantly increased both ANP mRNA and protein levels in the heart of CDH animals (P <.05).


CONCLUSIONS
The reduced cardiac ANP gene expression and ANP synthesis indicates that the heart in CDH is functionally immature and may be unable to respond to hemodynamic load accompanying persistent pulmonary hypertension (PPH). ANP or drugs such as steroids, which raise endogenous ANP levels, may have a therapeutic application in CDH complicated by PPH.
Guarino
N
N
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Shima
H
H
Puri
P
P
D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D006540:Herbicides / Q000009:adverse effects; D065630:Hernias, Diaphragmatic, Congenital; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010647:Phenyl Ethers / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005938:Glucocorticoids; D006540:Herbicides; D010647:Phenyl Ethers; D003907:Dexamethasone; D009320:Atrial Natriuretic Factor; C007350:nitrofen