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

[ Vol. 16 , Issue. 2 ]

Author(s):

Shuang-Quan Yu, Shuangtao Ma and Donna H. Wang*   Pages 148 - 155 ( 8 )

Abstract:


Background: Salt sensitivity is increased following renal Ischemia-Reperfusion (I/R) injury. We tested 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 a 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 were 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, capsaicin.

Affiliation:

Division of Nanomedicine and Molecular Intervention, Department of Medicine Michigan State University, East Lansing, Michigan, MI 48824, Division of Nanomedicine and Molecular Intervention, Department of Medicine Michigan State University, East Lansing, Michigan, MI 48824, Division of Nanomedicine and Molecular Intervention, Department of Medicine Michigan State University, East Lansing, Michigan, MI 48824

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