RT Journal Article
SR Electronic
T1 Angiotensin II Type 1 Receptor Antagonist Attenuates Lung Fibrosis in Hyperoxia-Exposed Newborn Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 169
OP 175
DO 10.1124/jpet.111.186288
VO 340
IS 1
A1 Hsiu-Chu Chou
A1 Yaw-Dong Lang
A1 Leng-Fang Wang
A1 Tzu-Ying Wu
A1 Yu-Fang Hsieh
A1 Chung-Ming Chen
YR 2012
UL http://jpet.aspetjournals.org/content/340/1/169.abstract
AB 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 (AT1R) antagonists and AT1R short interfering RNA diminished hyperoxia-increased collagen expression, whereas 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 7 days of >95% O2 and an additional 2 weeks of 60% O2. AT1R 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. AT1R 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. 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 for preventing hyperoxia-induced lung fibrosis.