Sodium nitrite prevents impaired postnatal alveolar development.

Area of Science:

• Biomedical Research
• Pulmonary Medicine
• Neonatology

Background:

• Nitric oxide (NO) deficiency is central to bronchopulmonary dysplasia (BPD) pathogenesis.
• Clinical trials of inhaled NO (iNO) for BPD prevention show limited efficacy.
• High NO reactivity can cause harmful oxidation and nitration, posing a challenge for NO-based therapies.

Purpose of the Study:

• To compare the preventive effects of sodium nitrite (NaNO2) and iNO in a rat model of experimental BPD.
• To investigate the impact of NaNO2 and iNO on lung morphology, NO signaling, and protein modifications.
• To determine if nitrite therapy offers advantages over iNO due to potentially lower adverse reaction risks.

Main Methods:

• A novel rat model of experimental BPD was established using hyperoxia-intermittent hypoxia (H-IH) exposure from postnatal days 1-21.
• Rat pups received daily subcutaneous (sc) NaNO2 or continuous iNO during H-IH exposure.
• Lung morphology, NO content and signaling, S-nitrosothiols (SNOs), and tyrosine nitration were assessed.

Main Results:

• H-IH induced alveolar and pulmonary vascular hypoplasia, pulmonary hypertension (PH), decreased NO signaling, and increased tyrosine nitration.
• NaNO2 treatment prevented abnormal lung morphology and PH, normalized NO signaling, and inhibited nitration.
• iNO prevented PH but had minimal effect on lung morphology and induced nitration in control animals.

Conclusions:

• Sodium nitrite (NaNO2) demonstrates superior efficacy over inhaled nitric oxide (iNO) in preventing experimental BPD.
• NaNO2 normalizes lung development and NO signaling while preventing harmful nitration.
• NaNO2 enhances protein S-nitrosylation, offering a potential biological rationale for its therapeutic advantage in BPD.