title: Angiotensin II type-1 receptor antagonist attenuates LPS-induced acute lung injury.
abstract: Angiotensin II is able to trigger inflammatory responses through an angiotensin II type 1 (AT1) receptor. The role of AT1 receptor in acute lung injury (ALI) is poorly understood. Mice were randomly divided into three groups (n=40 each groups): NS group; LPS group (2mg/kg LPS intratracheally); and LPS+ZD 7155 group, 10mg/kg ZD 7155 (an AT1 receptor antagonist) intraperitoneally 30 min prior to LPS exposure. Samples from the lung were isolated and assayed for histopathology analyses or proinflammatory gene expressions, angiotensin II receptors expressions and nuclear factors activities. LPS exposure resulted in severe ALI, elevated levels of TNF-alpha and IL-1 beta mRNA expressions, and increased activities of NF-kappaB and activated protein (AP)-1. Upregulation of AT1 receptor and down-regulation of AT2 receptor were also observed after LPS challenge. Pretreatment with ZD 7155 significantly inhibited the increase of AT1 receptor expression and upregulated AT2 receptor expression. ZD 7155 also reduced the mRNA expression of TNF-alpha and IL-1 beta, inhibited the activation of NF-kappaB and AP-1, and improved lung histopathology. These findings suggest that antagonism of AT1 receptor inhibits the activation of NF-kappaB and AP-1 in the lung, which may mediate the release of TNF-alpha and IL-1 beta and contribute to LPS-induced ALI.
authors.affiliation: Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Zhao-Fan
authors.initials: ZF
authors.lastname: Xia
authors.forename: Xu-Lin
authors.initials: XL
authors.lastname: Chen
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Jia
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009287:Naphthyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009287:Naphthyridines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C095905:ZD 7155