Article Text
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)-κB 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-κB 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.
- ACE, angiotensin converting enzyme
- ACE2, angiotensin converting enzyme 2
- AT1, AT2, types 1 and 2 angiotensin II receptors
- BAL, bronchoalveolar lavage
- JNK1, c-Jun N-terminal kinase 1
- MIP-2, macrophage inflammatory protein
- MPO, myeloperoxidase
- MV, mechanical ventilation
- NF-κB, nuclear factor-κB
- PCNA, proliferating cell nuclear antigen
- PEEP, positive end-expiratory pressure
- RAS, renin-angiotensin system
- RT-PCR, reverse transcription and polymerase chain reaction
- TNFα, tumour necrosis factor α
- VILI, ventilator-induced lung injury
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- ACE, angiotensin converting enzyme
- ACE2, angiotensin converting enzyme 2
- AT1, AT2, types 1 and 2 angiotensin II receptors
- BAL, bronchoalveolar lavage
- JNK1, c-Jun N-terminal kinase 1
- MIP-2, macrophage inflammatory protein
- MPO, myeloperoxidase
- MV, mechanical ventilation
- NF-κB, nuclear factor-κB
- PCNA, proliferating cell nuclear antigen
- PEEP, positive end-expiratory pressure
- RAS, renin-angiotensin system
- RT-PCR, reverse transcription and polymerase chain reaction
- TNFα, tumour necrosis factor α
- VILI, ventilator-induced lung injury
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Footnotes
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Published Online First 17 January 2007
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This study was supported by grants from the National Taiwan University Hospital (NTUH-94S97) and the National Science Council (NSC93-2314-B-002-223), Taiwan.
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Competing interests: None.