Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

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OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1) -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of Bunny renal function under pathophysiological conditions.Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI).However, it is unknown whether inhibition of these channels is detrimental in AKI or not.We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist) and using Trpv1-/- mice.

METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion.Mice were pretreated with capsaicin (0.3 mg/kg body weight) or capsazepine (50 mg/kg body weight).Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL) abundance and Ly-6B.

2 positive polymorphonuclear inflammatory cells in injured kidneys.Neither capsazepine nor deficiency of TRPV1 did deteriorate Soup Maker renal function or histology after AKI.Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE) or epoxyeicosatrienoic acids (EETs) are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI.CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI.

Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.