Inhaled ethyl nitrite prevents hyperoxia-impaired postnatal alveolar development in newborn rats (Publication with Expression of Concern. See vol. 200, pg. 1559, 2019)

Rationale: Inhaled nitric oxide (NO) has been used to prevent bronchopulmonary dysplasia, but with variable results. Ethyl nitrite (ENO) forms S-nitrosothiols more readily than does NO, and resists higher-order nitrogen oxide formation. Because S-nitrosylation is a key pathway mediating many NO biological effects, treatment with inhaled ENO may better protect postnatal lung development from oxidative stress than NO. Objectives: To compare inhaled NO and ENO on hyperoxia-impaired postnatal lung development. Methods: We treated newborn rats beginning at birth to air or 95% O-2 +/- 0.2-20.0 ppm ENO for 8 days, or to 10 ppm NO for 8 days. Pups treated with the optimum ENO dose, 10 ppm, and pups treated with 10 ppm NO were recovered in room air for 6 more days. Measurements and Main Results: ENO and NO partly prevented 95% O-2-induced airway neutrophil influx in lavage, but ENO had a greater effect than did NO in prevention of lung myeloperoxidase accumulation, and in expression of cytokine-induced neutrophil chemoattractant-1. Treatment with 10 ppm ENO, but not NO, for 8 days followed by recovery in air for 6 days prevented 95% O-2-induced impairments of body weight, lung compliance, and alveolar development. Conclusions: Inhaled ENO conferred protection superior to inhaled NO against hyperoxia-induced inflammation. ENO prevented hyperoxia impairments of lung compliance and postnatal alveolar development in newborn rats.