Ablation of TRPV1-positive nerves exacerbates salt-induced hypertension and tissue injury in rats after renal ischemia-reperfusion via infiltration of macrophages

High-salt intake after renal ischemia/reperfusion (I/R) injury leads to hypertension and further renal injury, but the mechanisms are largely unknown. This study tested the hypothesis that degeneration of transient receptor potential vanilloid 1 (TRPV1)-positive nerves exacerbates salt-induced hypertension and renal injury after I/R via enhancing renal macrophage infiltration. A large dose of capsaicin (CAP, 100 mg/kg, subcutaneously) was used to degenerate rat TRPV1-positive nerves. Then, rats were subjected to renal I/R injury and fed with a low-salt (0.4% NaCl) diet for 5 weeks after I/R, followed by a high-salt (4% NaCl) diet for 4 weeks during which macrophages were depleted using liposome-encapsulated clodronate (LC, 1.3 ml/kg/week, intravenously). The protein level of TRPV1 in the kidney was downregulated by renal I/R injury and was further decreased by CAP treatment. LC treatment did not affect the protein levels of renal TRPV1. After renal I/R injury, high-salt diet significantly increased renal macrophage infiltration, inflammatory cytokines (tumor necrosis factor alpha and interleukin 1 beta), systolic blood pressure, the urine/water intake ratio, plasma creatine and urea levels, urinary 8-isoprostane, and renal collagen deposition. Interestingly, CAP treatment further increased these parameters. These increases were abolished by depleting macrophages with LC treatment. These data suggest that degenerating TRPV1-positive nerves exacerbates salt-induced hypertension and tissue injury in rats after renal I/R injury via macrophages-mediated renal inflammation.