Prenatal treatment with nitrite reduces pulmonary arteriolar remodeling in neonates with congenital diaphragmatic hernia

Therapeutic use of alternative nitric oxide (NO) sources, such as nitrite and nitrate may be a protective influence on pulmonary vasculature abnormalities.

Aim

To evaluate whether the maternal administration of nitrite prevents the morphological and molecular changes that affect the pulmonary arterioles of congenital diaphragmatic hernia (CDH) neonates.

Methods

CEUA #88/2017. Sprague-Dawley neonate rats were divided into 6 groups: 1. control; 2. control + nitrite; 3. nitrofen exposed; 4. nitrofen exposed + nitrite; 5. CDH and 6. CDH + nitrite. The pregnant rats from nitrofen exposed and CDH groups were exposed to nitrofen on gestational day (GD) 9.5. The treatment with nitrite was made by gavage (15 mg/kg/day), on the last five gestational days. On GD 21.5 the fetuses were harvested. The following parameters were analyzed: lung and plasma nitrite concentration; media wall thickness (MWT) and endothelial NO synthase eNOS and inducible NO synthase iNOS immunohistochemistry of pulmonary arterioles.

Results

Nitrite treatment increased the maternal plasma concentration of nitrite in control and nitrofen-exposed rats. All neonates exposed to nitrofen showed an increase of nitrofen in the lung and plasma. Nitrite treatment decreased the MWT of pulmonary arterioles of CDH neonates. Nitrite treatment increased eNOS marker and attenuated iNOS marker in neonates with CDH.

Conclusions

Nitrite maternal treatment rescued the morphometry and recovered eNOS expression of CDH pulmonary arterioles during CDH. Nitrite is a potential prenatally therapeutic approach to vascular alterations present in CDH neonates.