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

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; capsaicin; renal ischemia/reperfusion; salt intake; sympathetic nervous system.

Fig. (1)

Representative Western blots showing TRPV1 expression in the kidney 4 weeks after high-salt feeding in rats with renal ischemia-reperfusion (I/R) injury and capsaicin pre-treatment (A). (B) Quantification results (% β-actin arbitrary units). Values are mean ± SE (n = 5). *p<0.05 compared with the sham group; †p<0.05 compared with the I/R group.

Fig. (2)

Effects of ischemia/reperfusion (I/R), capsaicin pre-treatment and high salt feeding on blood pressure in rats. (A) Systolic 
blood pressure was measured once a week before and after I/R. (B) Mean arterial pressure (MAP) was measured at 9 weeks after I/R or 
at 4 weeks after high salt loading. Values are mean ± SE (n = 5-7). *p<0.05 compared with the sham group; †p<0.05 compared with the I/R group.

Fig. (3)

Effects of I/R, capsaicin pretreatment and high-salt feeding on the 24-hour ratio of urine/water intake (A), creatinine clearance 
(B) and plasma urea (C) in rats. Values are mean ± SE (n = 6-8). *p<0.05 compared with the sham group; †p<0.05 compared with the I/R group.

Fig. (4)

Sympathetic and afferent renal nerve activity. (A) Renal sympathetic nerve activity after intrathecal injection of muscimol at the end of the experiments. (B) Urinary norepinephrine levels before and 4 weeks after high salt loading in rats with I/R and capsaicin pretreatment. (C) Afferent renal nerve activity after intra-pelvis injection of capsaicin. Values are mean ± SE (n = 5-6). *p<0.05 compared with the sham group; †p<0.05 compared with the I/R group.