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.
- lung injury
- mechanical ventilation
- renin-angiotensin system