Angiotensin II type 1 receptor antagonist attenuates lung fibrosis in hyperoxia-exposed newborn rats

Hsiu Chu Chou, Yaw Dong Lang, Leng-Fang Wang, Tzu Ying Wu, Yu Fang Hsieh, Chung Ming Chen

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16 Citations (Scopus)

Abstract

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 is up-regulated in human lung fibroblasts. Angiotensin II type 1 receptor (AT 1R) antagonists and AT 1R short interfering RNA diminished hyperoxia-increased collagen expression, whereas AT 2R antagonists did not have any effects on these hyperoxia-induced changes. The in vivo therapeutic effects of AT 1R antagonists on hyperoxia-induced lung fibrosis remain unknown. The present study assessed the effects of an AT 1R antagonist (losartan) on preventing hyperoxia-induced lung fibrosis in newborn rats. Rat pups were exposed to 7 days of >95% O 2 and an additional 2 weeks of 60% O 2. AT 1R antagonist-treated pups were injected intraperitoneally with losartan at a dose of 10 mg/kg/day from postnatal days 1 to 7 and a dose of 5 mg/kg/day from postnatal days 8 to 21. Control group pups were injected with an equal volume of normal saline. AT 1R antagonist treatment attenuated the hyperoxia-induced lung fibrosis on postnatal days 7 and 21 and also decreased the hyperoxia-induced expression of extracellular signal-regulated protein kinase and α-smooth muscle actin. AT 1R antagonist treatment did not affect body weight or lung weight of the rats. These data suggest that AT 1R antagonist may offer a novel therapeutic strategy for preventing hyperoxia-induced lung fibrosis.

Original languageEnglish
Pages (from-to)169-175
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume340
Issue number1
DOIs
Publication statusPublished - Jan 2012

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ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

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