• Qian Chen, Bin Yi, Jianbo Ma, Jiaoling Ning, Lingzhi Wu, Daqing Ma, Kaizhi Lu, and Jianteng Gu.
• Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China.
• Oncotarget. 2016 Aug 30; 7 (35): 55990-56001.

AbstractRenal ischemia-reperfusion (rI/R) could cause remote acute lung injury (ALI) and combination of these two organ injuries can remarkably increase the mortality. This study aims to determine whether dexmedetomidine, an α2-adrenoreceptor agonist sedative, can ameliorate pulmonary microvascular hyper-permeability following rI/R injury and explore the underlying mechanisms. In vivo, C57BL/6J mice received dexmedetomidine (25µg/kg, i.p.) in the absence or presence of α2-adrenergic antagonist atipamezole (250µg/kg, i.p.) or focal adhesion kinase (FAK) inhibitor (30mg/kg, i.p.) before bilateral renal pedicle clamping for 45 minutes followed by 24 hours reperfusion. The lung histopathological changes and the permeability of pulmonary microvascular were assessed respectively. In vitro, the cultured C57BL/6J mice pulmonary microvascular endothelial cells (PMVECs) were treated with serum from mice with rI/R with or without dexmedetomidine and atipamezole. Trans-endothelial permeability and phospho-tyrosine397FAK, F-actin, VE-cadherin and ZO-1 in monolayer PMVECs were measured respectively in the presence or absence of rI/R serum, dexmedetomidine and FAK inhibitor. In vivo, dexmedetomidine remarkably attenuated lung injury and pulmonary microvascular hyper-permeability caused by rI/R injury, which was abolished by atipamezole or FAK inhibitor co-administration. In vitro, the permeability of PMVECs monolayer following exposure to serum from rI/R mice was increased significantly, and decreased by dexmedetomidine. Dexmedetomidine increased phospho-tyrosine397FAK in a time- and dose-dependent manner, which was correlated with the changes in trans-endothelial permeability. Our data indicated that dexmedetomidine is able to ameliorate remote pulmonary microvascular hyper-permeability induced by rI/R, at least in part, via FAK modulation.

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