TRPV1 protects renal ischemia-reperfusion injury in diet-induced obese mice by enhancing CGRP release and increasing renal blood flow

Background: Obesity is a major risk factor for end-stage renal disease. Using transient receptor potential vanilloid 1 knockout (TRPV1(-/-)) mice, we tested the hypothesis that TRPV1 protects against obesity-induced exacerbation of renal ischemia-reperfusion (I/R) injury. Methods: TRPV1(-/-) and wild-type (WT) mice were fed a chow or Western diet (WD) for 22-23 weeks. After that, mice were subjected to renal I/R injury, and renal cortical blood flow (CBF) and medullary blood flow (MBF) were measured. Results: The Western diet significantly increased body weight and fasting blood glucose levels in both TRPV1(-/-) and WT mice. WD-induced impairment of glucose tolerance was worsened in TRPV1(-/-) mice compared with WT mice. WD intake prolonged the time required to reach peak reperfusion in the cortex and medulla (both P < 0.05), decreased the recovery rate of CBF (P < 0.05) and MBF (P < 0.05), and increased blood urea nitrogen, plasma creatinine, and urinary 8-isoprostane levels after I/R in both mouse strains, with greater effects in TRPV1(-/-) mice (all P < 0.05). Renal I/R increased calcitonin gene-related peptide (CGRP) release in WT but not in TRPV1(-/-) mice, and WD attenuated CGRP release in WT mice. Moreover, blockade of CGRP receptors impaired renal regional blood flow and renal function in renal I/R injured WT mice. Conclusion: These results indicate that TRPV1 plays a protective role in WD-induced exacerbation of renal I/R injury probably through enhancing CGRP release and increasing renal blood flow.