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We evaluated the effect of capsaicin, one of the transient receptor potential vanilloid receptor 1 (TRPV1) agonists, on ischemic acute renal failure (ARF) in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 minutes followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function in vehicle-treated ARF rats markedly decreased at 24 hours after reperfusion. Treatment with capsaicin (3, 10, and 30 mg/kg, orally) 30 minutes before ischemia dose-dependently attenuated ischemia/reperfusion-induced renal dysfunction. In renal tissues exposed to ischemia/reperfusion, neutrophil infiltration, renal superoxide production, and renal tumor necrosis factor (TNF)-α mRNA expression were augmented, but these alterations were attenuated by the treatment with capsaicin. On the other hand, ischemia/reperfusion-enhanced renal interleukin (IL)-10 mRNA expression and plasma concentrations of IL-10 were augmented by treatment with capsaicin in ARF rats. In addition, resiniferatoxin (20 μg/kg, subcutaneous), a more selective and potent TRPV1 agonist, showed a renoprotective effect on ischemia/reperfusion-induced renal injury, in a qualitatively similar way to cases seen with capsaicin. These results demonstrate that TRPV1 agonists prevent ischemia/reperfusion-induced renal dysfunction. These renoprotective effects seem to be closely related to the inhibition of inflammatory response via TRPV1.