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- Xiaolin He, Bing Han, Marco Mura, Shuyue Xia, Shi Wang, Tao Ma, Mingyao Liu, and Zhi Liu.
- Department of Emergency and Institute of Respiratory Disease, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.
- Shock. 2007 Jul 1;28(1):106-11.
AbstractLack of specific and efficient therapy leads to the high mortality rate of acute lung injury (ALI) and acute respiratory distress (ARDS). Recent evidence implies that angiotensin-converting enzyme (ACE) plays an important role in the pathogenesis of ALI. Pharmaceutical inhibitors of ACE have been used clinically for hypertension but not for ALI/ARDS yet. The objective was to study the effects of ACE inhibition with captopril on severe lung injury induced by oleic acid (OA) in rats. Oleic acid was intravenously injected into Sprague Dawley rats, followed by i.p. administration of captopril or saline control. Lung injury, endothelium damage and related molecules, and disturbance of coagulation were examined in comparison between the treated and the nontreated groups. An OA-induced ALI was featured with thickening of the alveolar septa, alveolar hemorrhage, and infiltration of inflammatory cells. Comparing with the nontreated OA group, the administration of captopril prevented the rats from OA-induced severe lungs injury, with a significantly lower lung injury score, less albumin content and infiltrated cells in the alveoli, decreased wet/dry weight ratio of the lung tissues, and improved lung function (PaO2 per fraction of inspired oxygen). Captopril also dramatically reduced the expression of intercellular adhesion molecule-1 in the lung tissue and in the circulating endothelial cells in the blood, indicating a protective effect on endothelial cells activation/damage. Moreover, captopril treatment led to a blockage of nuclear factor kappaB activation in lung tissues and to the recovery of the fibrinolytic disturbance. Thus, our data suggest that the inhibition of ACE with its clinically used inhibitor offers protective effects on ALI/ARDS, implying the potential for therapeutic option.
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