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)-kappa B 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-kappa 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. 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.