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.