Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity and mortality during the first year of life, and many infants have significant respiratory problems throughout childhood. Currently no effective therapy is clinically available to prevent the long-term pulmonary sequelae of BPD. Previous research has demonstrated that the renin-angiotensin system (RAS) is upregulated in human lung fibroblasts. Angiotensin II type 1 receptor (AT1R) antagonists and AT1R siRNA diminished hyperoxia-increased collagen expression, while AT2R antagonists did not have any effects on these hyperoxia-induced changes. The in vivo therapeutic effects of AT1R antagonists on hyperoxia-induced lung fibrosis remain unknown. The present study assessed the effects of an AT1R antagonist (losartan) on preventing hyperoxia-induced lung fibrosis in newborn rats. Rat pups were exposed to seven days of >95 % O2 and a further two weeks of 60 % O2. AT1R antagonist-treated pups were injected intraperitoneally with losartan at a dose of 10 mg/kg/day from postnatal days one to seven, and 5 mg/kg/day from postnatal days eight to 21. Control group pups were injected with an equal volume of normal saline. AT1R antagonist treatment attenuated the hyperoxia-induced lung fibrosis on postnatal days seven and 21, and also decreased the hyperoxia-induced expression of extracellular signal-regulated protein kinase and alpha-smooth muscle actin. AT1R antagonist treatment did not affect body weight or lung weight of the rats. These data suggest that AT1R antagonist may offer a novel therapeutic strategy to prevent hyperoxia-induced lung fibrosis.
- Received July 25, 2011.
- Revision received October 9, 2011.
- Accepted October 14, 2011.
- The American Society for Pharmacology and Experimental Therapeutics