title: Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.
abstract: OBJECTIVE
  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 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.
  
  
  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 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.
authors.affiliation: Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine (MDC), Lindenberger Weg 80, Berlin, Germany; Xiamen Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine (MDC), Lindenberger Weg 80, Berlin, Germany.
authors.forename: Lajos
authors.initials: L
authors.lastname: Markó
authors.affiliation: Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine (MDC), Lindenberger Weg 80, Berlin, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Kaßmann
authors.affiliation: Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine (MDC), Lindenberger Weg 80, Berlin, Germany; Medical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow, Augustenburger Platz 1, Berlin, Germany.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Pathology, Charité Campus Mitte, Charitéplatz 1, Berlin, Germany.
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Wu
authors.affiliation: Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine (MDC), Lindenberger Weg 80, Berlin, Germany; Medical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow, Augustenburger Platz 1, Berlin, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Gollasch
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015777:Eicosanoids / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C071423:capsazepine; D002211:Capsaicin