OBJECTIVEIn addition to regulating blood pressure, angiotensin II is involved in lung fibrogenesis. This study aimed to explore the effect of losartan, an angiotensin II type 1 receptor antagonist, on lung fibrosis in neonatal rats with hyperoxia-induced chronic lung disease (CLD) and its possible mechanisms.

METHODSNeonatal Wistar rats were randomly divided into four groups within 24 hrs after birth: room air exposure, hyperoxia exposure (85%-90% O2), hyperoxia exposure + losartan, and hyperoxia exposure + placebo. Losartan (5 mg/kg/d) or placebo was administered beginning on the 6th day after birth. After 7, 14 and 21 days of exposure, 8 rats in each group were sacrificed. Lung histological changes were evaluated by hematoxylin-eosin staining. Levels of hydroxyproline (HYP), superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissues were determined by spectroscopy.

RESULTSHyperoxia exposure resulted in decreased alveolar septation, enlarged terminal air space, increased collagen deposition, pulmonary hemorrhage, and pulmonary consolidation. In the hyperoxia exposure + losartan group, the alveolar septum became thinner and lung fibrosis was alleviated, but the alveolar space was not obviously deflated and the number of secondary septum was not increased. Hyperoxia exposure increased significantly the HYP contents in lung tissues 14 and 21 days after exposure. Addition of losartan to the hyperoxia exposure resulted in decreased HYP contents (471.46 +/- 30.63 mu g/kg vs 545.15 +/- 34.90 mu g/kg for hypoxia alone; P < 0.01) after 21 days of exposure. SOD activity increased 7 days after hyperoxia exposure and then decreased to levels similar to the air exposure group. MDA levels increased to a peak at 7 days and remained at higher levels through 21 days of exposure when compared with the air exposure group (P < 0.01). Losartan treatment significantly increased SOD activities (82.94 +/- 4.62 U/mg protein vs 67.78 +/-8.02 U/mg protein; P < 0.01) and decreased MDA levels (30.54 +/- 5.89 nmol/mg protein vs 48.75 +/- 8.09 nmol/mg protein, P < 0.01) compared with the hyperoxia exposure group 21 days after exposure.

CONCLUSIONSLosartan attenuated lung fibrosis in neonatal rats with hyperoxia-induced CLD, possibly through an increase of antioxidase enzyme activity and reduction of lipid peroxidation.