Dexmedetomidine attenuates remote lung injury induced by renal ischemia-reperfusion in mice

Background: Renal ischemia-reperfusion (I/R) may cause acute lung injury (ALI). The mortality of combined acute kidney injury and ALI is extremely high. Dexmedetomidine, an alpha(2) adrenergic agonist, exerts potent anti-inflammatory and organoprotective effects in addition to its sedative and analgesic properties. We sought to elucidate whether dexmedetomidine can attenuate lung injury following renal I/R in a murine model of renal I/R. Methods: Adult C57BL/6J male mice were randomized to five groups: sham-operated control (Sham); renal I/R (I/R); intraperitoneal injection of dexmedetomidine 25 mu g/kg before ischemia (pre-dex) and after perfusion (post-dex); combination of alpha(2) adrenergic antagonist atipamezole 250 mu g/kg prior to dexmedetomidine pre-treatment (atip-dex). Kidney I/R was induced by bilateral renal pedicle clamping for 45 min and followed by 6 h reperfusion. The pulmonary tissues were harvested for histopathological evaluation, wet/dry ratio measurement, biochemical analysis of myeloperoxidase (MPO), Polymerase chain reaction (PCR) determination of Inter-cellular adhesion molecule (ICAM-1) and Tumor necrosis factor - alpha (TNF-alpha) mRNA. Results: Renal IR induced significant pulmonary injuries, increased wet/dry ratio together with the enhanced of MPO activities and increased ICAM-1 and TNF-alpha mRNA level. Both pre- and post-treatment with dexmedetomidine markedly reduced lung edema and inflammatory response and lowered MPO activity and ICAM-1 and TNF-alpha mRNA expression. The protective effects of dexmedetomidine in the lung were partially reversed by atipamezole, but there were no effect on ICAM-1 and TNF-alpha mRNA expression level. Conclusions: Dexmedetomidine is capable of attenuating remote lung injury induced by renal IR via both alpha(2) adrenoceptors dependent and independent mechanisms.