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TRPV1 Activation Prevents Renal Ischemia-reperfusion Injury-induced Increase in Salt Sensitivity by Suppressing Renal Sympathetic Nerve Activity

Author(s):

Shuang-Quan Yu, Shuangtao Ma and Donna H. Wang*   Pages 1 - 8 ( 8 )

Abstract:


Background: Salt sensitivity is increased following renal ischemia-reperfusion (I/R) injury. We test the hypothesis that high-salt intake-induced increase in renal sympathetic nerve activity (RSNA) after renal I/R can be prevented by activation of transient receptor potential vanilloid 1 (TRPV1).

Methods: Rats were fed a 0.4% NaCl diet for 5 weeks after renal I/R, followed by a 4% NaCl diet for 4 more weeks in four groups: sham, I/R, I/R+high dose capsaicin (HDC), and I/R+low dose capsaicin (LDC). The low (1mg/kg) or high (100mg/kg) dose of capsaicin was injected subcutaneously before I/R to activate or desensitize TRPV1, respectively.

Results: Systolic blood pressure was gradually elevated after fed on high-salt diet in the I/R and I/R+HDC groups but not in the I/R+LDC group, with a greater increase in the I/R+HDC group. Renal function was impaired in the I/R group and was further deteriorated in the I/R+HDC group but was unchanged in the I/R+LDC group. At the end of high salt treatment, afferent renal nerve activity in response to unilateral intra-pelvic administration of capsaicin was decreased in the I/R group and was further suppressed in the I/R+HDC group but was unchanged in the I/R+LDC group. RSNA in response to intrathecal administration of muscimol, a selective agonist of GABA-A receptors, was augmented in the I/R group and further intensified in the I/R+HDC group but was unchanged in the I/R+LDC group. Similarly, urinary norepinephrine levels were increased in the I/R group and was further elevated in the I/R+HDC group but unchanged in the I/R+LDC group.

Conclusion: These data suggest that TRPV1 activation prevents renal I/R injury-induced increase in salt sensitivity by suppressing RSNA.

Keywords:

TRPV1, blood pressure, renal ischemia/reperfusion, salt intake, sympathetic nervous system

Affiliation:

Division of Nanomedicine and Molecular Intervention, Department of Medicine, Division of Nanomedicine and Molecular Intervention, Department of Medicine, Division of Nanomedicine and Molecular Intervention, Department of Medicine



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