Activation of TRPV1-Expressing Renal Sensory Nerves of Rats with N-Oleoyldopamine Attenuates High-Fat-Diet-Induced Impairment of Renal Function.

Abstract

Enhanced renal sympathetic nerve activity (RSNA) contributes to obesity-induced renal disease, while the role of afferent renal nerve activity (ARNA) is not fully understood. The present study tested the hypothesis that activating the transient receptor potential vanilloid 1 (TRPV1) channel in afferent renal nerves suppresses RSNA and prevents renal dysfunction and hypertension in obese rats. N-oleoyldopamine (OLDA, 1 ng/kg, daily) was administrated intrathecally (T8-L3) via an indwelled catheter to chronically activate, TRPV1-positive afferent renal nerves in rats fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD intake significantly increased the body weight, impaired glucose and insulin tolerance, decreased creatinine clearance, and elevated systolic blood pressure in rats compared with the levels of the chow-fed rats (all p < 0.05). An intrathecal OLDA treatment for 8 weeks did not affect the fasting glucose level, glucose tolerance, and insulin tolerance in rats fed either chow or HFD. As expected, the chronic OLDA treatment significantly increased the levels of plasma calcitonin gene-related peptide and substance P and ARNA in the HFD-fed rats (all p < 0.05). Interestingly, the OLDA treatment decreased the urinary norepinephrine level and RSNA in rats fed HFD (both p < 0.05). Importantly, the OLDA treatment attenuated HFD-induced decreases in creatinine clearance and urinary Na+ excretion and increases in the plasma urea level, urinary albumin level, and systolic blood pressure at the end of an 8-week treatment (all p < 0.05). Taken together, the intrathecal administration of OLDA ameliorates the enhancement of RSNA, renal dysfunction, and hypertension in obese rats. These findings shed light on the roles of TRPV1-positive renal afferent nerves in obesity-related renal dysfunction and hypertension.