title: Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model.
abstract: BACKGROUND
  Injurious mechanical ventilation can cause a pro-inflammatory reaction in the lungs. Recent evidence suggests an association of the renin-angiotensin system (RAS) with lung inflammation. A study was undertaken to investigate the pathogenic role of the RAS in ventilator-induced lung injury (VILI) and to determine whether VILI can be attenuated by angiotensin converting enzyme (ACE) inhibition.
  
  
  METHODS
  Male Sprague-Dawley rats were mechanically ventilated for 4 h with low (7 ml/kg) or high (40 ml/kg) tidal volumes; non-ventilated rats were used as controls. Lung injury and inflammation were measured by the lung injury score, protein leakage, myeloperoxidase activity, pro-inflammatory cytokine levels and nuclear factor (NF)-kappaB activity. Expression of the RAS components was also assessed. Some rats were pretreated with the ACE inhibitor captopril (10 mg/kg) for 3 days or received a concomitant infusion with losartan or PD123319 (type 1 or type 2 angiotensin II receptor antagonist) during mechanical ventilation to assess possible protective effects on VILI.
  
  
  RESULTS
  In the high-volume group (n=6) the lung injury score, bronchoalveolar lavage fluid protein concentration, pro-inflammatory cytokines and NF-kappaB activities were significantly increased compared with controls (n=6). Lung tissue angiotensin II levels and mRNA levels of angiotensinogen and type 1 and type 2 angiotensin II receptors were also significantly increased in the high-volume group. Pretreatment with captopril or concomitant infusion with losartan or PD123319 in the high-volume group attenuated the lung injury and inflammation (n=6 for each group).
  
  
  CONCLUSIONS
  The RAS is involved in the pathogenesis of ventilator-induced lung injury. ACE inhibitor or angiotensin receptor antagonists can attenuate VILI in this rat model.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, No 7 Chung-Shan South Road, Taipei 100, Taiwan.
authors.forename: Jih-Shuin
authors.initials: JS
authors.lastname: Jerng
authors.forename: Yu-Chiao
authors.initials: YC
authors.lastname: Hsu
authors.forename: Huey-Dong
authors.initials: HD
authors.lastname: Wu
authors.forename: Hong-Zhen
authors.initials: HZ
authors.lastname: Pan
authors.forename: Hao-Chien
authors.initials: HC
authors.lastname: Wang
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002216:Captopril / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*; D012121:Respiration, Artificial / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012122:Ventilators, Mechanical
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D002216:Captopril