Activation of TRPV1 prevents salt-induced kidney damage and hypertension after renal ischemia-reperfusion injury in rats

Abstract

Background/Aims: High-salt intake after recovery from renal ischemia-reperfusion (I/R) injury leads to hypertension with severe renal damage. Transient receptor potential vanilloid type 1 (TRPV1) channels have been involved in the regulation of inflammation and oxidative stress following ischemic organ injury. We tested the hypothesis that activation of TRPV1 conveys preconditioning protection to the kidney subjected to I/R. Methods: TRPV1 was activated or down-regulated by subcutaneous injection of a low (1mg/kg) or high (100mg/kg) dose of capsaicin, respectively, 3 hours before ischemia. Rats were fed a 0.4% NaCl diet for 5 weeks after I/R followed by a 4% NaCl diet for 4 more weeks in 4 groups: sham, I/R, I/R+high-dose capsaicin (HCap), and I/R+low-dose capsaicin (LCap). Results: Renal TRPV1 expression was decreased in I/R rats (P< 0.05) and further reduced in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap rats compared with the sham group. Blood pressure were elevated in I/R rats (P< 0.05) and further increased in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap rats compared with sham. Renal function was impaired in I/R rats (P< 0.05) and further deteriorated in I/R+HCap group (P< 0.05) but unchanged in I/R+LCap group. Renal inflammatory responses, oxidative stress, and renal collagen deposition were augmented in I/R rats (all P< 0.05) and further intensified in I/R+HCap group (all P< 0.05) but unchanged in I/R+LCap group. Conclusion: Activation of TRPV1 plays an anti-inflammatory and anti-oxidative stress role in preventing renal tissue damage and salt-induced hypertension after I/R injury, indicating that TRPV1 conveys preconditioning protection that may have therapeutic implication.