Abstract：OBJECTIVE: To investigate the role of endogenous nitric oxide (NO) in hyperoxiainduced lung injury, by studying the effect of hyperoxia on NO synthesis and nitric oxide synthase (NOS) expression in the lung of preterm rats. METHODS: Threedayold preterm rats were randomly assigned to a hyperoxia group (90% oxygen) and room air group. After 3 days or 7 days of exposure, the ratio of lung wet weight/dry weight (W/D), lung morphometry, NO content in bronchoalveolar lavage fluid (BALF), and the cellular distribution and expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in the lung were measured. RESULTS: After 3 days of exposure, when compared with the control group, the hyperoxia group showed acute lung injury characterized by the presence of hyperaemia, red cell extravasation, and inflammatory infiltration. After 7 days of exposure, W/D was also increased in the hyperoxia group compared to the controls (5.54±0.41 VS 5.00±0.15, P<0.05), in addition to the pathologic changes. After 3 and 7 days of exposure, the NO content in BALF was significantly elevated in the hyperoxia group compared with that of the air group ［(17.06±5.86) μmol/L vs (5.59±2.03) μmol/L and (23.75±4.07) μmol/L vs (7.93±2.33) μmol/L, respectively, P<0.01］. In the lungs of the hyperoxia group, immunostaining for iNOS was observed in the airway and alveolar epithelium, and in inflammatory cells, to a greater degree than in the air group. The expression of iNOS in rats was stronger after 7 days of hyperoxic exposure than after 3 days. After 7 days of exposure, stronger immunostaining for eNOS in the airway epithelium of the hyperoxia group than of the air group was seen. CONCLUSIONS: Hyperoxia can significantly upregulate the expression of iNOS and eNOS in inflammatory cells and epithelium in the lungs of preterm rats and thus promote NO generation, suggesting that endogenous NO may mediate hyperoxiainduced pulmonary injury.
