Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model.
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.
Jerng
Jih-Shuin
JS
Department of Internal Medicine, National Taiwan University Hospital, No 7 Chung-Shan South Road, Taipei 100, Taiwan.
Hsu
Yu-Chiao
YC
Wu
Huey-Dong
HD
Pan
Hong-Zhen
HZ
Wang
Hao-Chien
HC
Shun
Chia-Tung
CT
Yu
Chong-Jen
CJ
Yang
Pan-Chyr
PC
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D016328:NF-kappa B; D012333:RNA, Messenger; D002216:Captopril