title: Role of asymmetric dimethylarginine in acute lung injury induced by cerebral ischemia/reperfusion injury in rats.
abstract: OBJECTIVE
  To determine the role of asymmetric dimethylarginine (ADMA) in acute lung injury induced by cerebral ischemia/reperfusion (I/R) injury in rats.
  
  
  METHODS
  Adult male SD rats were randomly divided into 4 groups, namely the sham-operated group (S), cerebral I/R model group, ADMA+I/R group, and dimethylarginine dimethylaminohydrolase (DDAH)+I/R group. In the latter 3 groups, acute lung injury was induced by left middle cerebral artery occlusion for 120 min. After a 24-h reperfusion, the rats were sacrificed and the activities of nitric oxide synthase (NOS) and contents of nitric oxide (NO) were measured using reductase and colorimetric assay. The mRNA and protein expressions of protein kinase C (PKC) and myosin light chain kinase (MLCK) in the lung tissues were detected with RT-PCR and Western blotting, respectively. The contents of ADMA in the bronchoalveolar lavage fluid (BALF) and blood flowing into and out of the lungs were measured by ELISA.
  
  
  RESULTS
  Cerebral I/R injury caused significantly elevated ADMA levels in the BALF and blood flowing into the lungs, and obviously lowered the NO concentration and NOS activity in the lung tissues (P<0.05). Following cerebral I/R injury, MLCK and PKC mRNA and protein expressions were significantly upregualted in the lung tissues (P<0.05). Exogenous DDAH obviously decreased the levels of ADMA in the BALF and blood flowing into the lungs, increased NO concentration and NOS activity, and down-regulated MLCK and PKC mRNA and protein expressions in lung tissues of rats with cerebral I/R injury (P<0.05).
  
  
  CONCLUSIONS
  ADMA contributes to the development of acute lung injury following cerebral I/R injury in rats by upregulating MLCK and PKC expression. ADMA may serve as a novel therapeutic biomarker and a potential therapeutic target for acute lung injury induced by cerebral I/R injury.
authors.affiliation: Kunming Medical University, Kunming 650031, China. wuyunhu00@sina.com
authors.forename: Yun-hu
authors.initials: YH
authors.lastname: Wu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Dian-hua
authors.initials: DH
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002545:Brain Ischemia / Q000150:complications; D008297:Male; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase