alpha-2-Adrenergic agonists protect against radiocontrast-induced nephropathy in mice

摘要

First published June 25, 2008; doi:10.1152/ajprenal.90244.2008.-Radiocontrast nephropathy (RCN) is a common clinical problem for which there is no effective therapy. Utilizing a murine model, we tested the hypothesis that a2-adrenergic receptor agonists (clonidine and dexmedetomidine) protect against RCN induced with iohexol (a nonionic low-osmolar radiocontrast). 857BL/6 mice were pretreated with saline, clonidine, or dexmedeto-midine before induction of RCN. Some mice were pretreated with yohimbine (a selective a2-receptor antagonist) before saline, clonidine, or dexmedetomidine administration. ct2-Agonist-treated mice had reduced plasma creatinine, renal tubular necrosis, renal apoptosis, and renal cortical proximal tubule vacuolization 24 h after iohexol injection. Yohimbine reversed the protective effects of clonidine and dexmedetomidine pretreatment. Injection of iohexol resulted in arapid(-~90min) fall of renal outer medullary blood flow. Clonidine and dexmedetomidine pretreatment significantly attenuated this perfusion decrease without changing systemic blood pressure. To determine whether proximal tubular a2-adrenergic receptors mediate the cytoprotective effects, we treated cultured human proximal tubule (HK-2) cells and rat pulmonary microvascular endothelial cells with iohexol after vehicle, clonidine, or dexmedetomidine pretreatment. Iohexol caused a direct dose-dependent reduction of HK-2 and rat pulmonary microvascular endothelial cell viability, but a2-agonists failed to preserve the viability of both cell types. We conclude that alpha2-adrenergic receptor agonists protect mice against RCN by preserving outer medullary renal blood flow. As a2-agonists are widely utilized during the perioperative period, our findings may have significant clinical relevance to improving outcomes following radiocontrast exposure.