atrial-natriuretic-factor and nitrofen

Many infants with congenital diaphragmatic hernias (CDHs) experience persistent pulmonary hypertension that is refractory to treatment with inhaled nitric oxide (NO). We have examined the responses of isolated pulmonary arterioles from prenatal and postnatal rats with and without nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether)-induced CDH to a variety of activators of the NO-cyclic guanosine monophosphate (cGMP) pathway.. Right-sided CDH was induced in fetal rats by feeding nitrofen to pregnant rats on day 12 of gestation. Control rats were fed olive oil (vehicle). Third-generation pulmonary arterioles were isolated from the right lung of prenatal rats at term and from newborn rats within 8 hours after birth. Responses to increasing concentrations of sodium nitroprusside (SNP), atrial natriuretic peptide, or 8-bromo-cGMP were measured in pulmonary arterioles from control rats and from rats with nitrofen-induced CDH. Postnatal responses to 8-bromo-cGMP were also recorded in the presence of zaprinast, a type V phosphodiesterase inhibitor.. Pulmonary arterioles from prenatal rats did not dilate in response to SNP, atrial natriuretic peptide, or 8-bromo-cGMP. Vasodilatory responses of postnatal pulmonary arterioles from control rats to SNP and 8-bromo-cGMP were significantly greater than for arterioles from rats with CDH. Zaprinast pretreatment resulted in similar responses for postnatal CDH and control arterioles to 8-bromo-cGMP.. Postnatal pulmonary arterioles from CDH rats exhibit altered nitrovasodilator responsiveness, which may be due to rapid degradation of cGMP.

Topics: Animals; Arterioles; Atrial Natriuretic Factor; Cyclic GMP; Disease Models, Animal; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Hypertension, Pulmonary; Lung; Nitric Oxide; Nitroprusside; Pesticides; Phenyl Ethers; Phosphodiesterase Inhibitors; Purinones; Rats; Rats, Sprague-Dawley; Vasodilation; Vasodilator Agents

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.. 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.. 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).. 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.

Topics: Animals; Animals, Newborn; Atrial Natriuretic Factor; Dexamethasone; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gene Expression; Glucocorticoids; Herbicides; Hernias, Diaphragmatic, Congenital; Hypertension, Pulmonary; Myocardium; Phenyl Ethers; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction