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Role of the renin-angiotensin system in ventilator- induced lung injury: An in vivo study in a rat model
  1. Jih-Shuin Jerng (jsjerng{at}ntumc.org)
  1. Department of Internal Medicine, National Taiwan University Hospital, Taiwan
    1. Yu-Chiao Hsu (felicite37{at}yahoo.com.tw)
    1. Department of Internal Medicine, National Taiwan University Hospital, Taiwan
      1. Huey-Dong Wu (hdwu{at}ha.mc.ntu.edu.tw)
      1. Department of Internal Medicine, National Taiwan University Hospital, Taiwan
        1. Hong-Zhen Pan (iris0542{at}yahoo.com.tw)
        1. Department of Internal Medicine, National Taiwan University Hospital, Taiwan
          1. Hao-Chien Wang (hcwang{at}ha.mc.ntu.edu.tw)
          1. Department of Integrated Diagnostic & Therapeutics, National Taiwan University Hospital, Taiwan
            1. Chia-Tung Shun (shun{at}ha.mc.ntu.edu.tw)
            1. Department of Forensic Medicine, National Taiwan University Hospital, Taiwan
              1. Chong-Jen Yu (jeffery{at}ha.mc.ntu.edu.tw)
              1. Department of Internal Medicine, National Taiwan University Hospital, Taiwan
                1. Pan-Chyr Yang (pcyang{at}ha.mc.ntu.edu.tw)
                1. Department of Internal Medicine, National Taiwan University Hospital, Taiwan

                  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. We investigated the pathogenic role of the RAS in ventilator-induced lung injury (VILI) and whether VILI can be attenuated by angiotensin-converting enzyme (ACE) inhibition.

                  Methods: Male Sprague-Dawley rats were mechanically ventilated for 4 hours with low (7 ml/kg) or high (40 ml/kg) tidal volumes, while non-ventilated rats were used as controls. Lung injury and inflammation were measured by lung injury score, protein leak, myeloperoxidase activity, pro-inflammatory cytokine levels, nuclear factor(NF)-κB activity. Expression of the RAS components was also assessed. Some rats were pre-treated with the ACE inhibitor captopril (10 mg/kg) for three days or received 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-κ B 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. Pre-treatment 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.

                  • captopril
                  • inflammation
                  • lung injury
                  • mechanical ventilation
                  • renin-angiotensin system

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