Effects of a high-salt diet on TRPV-1-dependent renal nerve activity in Dahl salt-sensitive rats

Abstract

Objective: To test the hypothesis that transient receptor potential vanilloid type 1 channel (TRPV1)-mediated increases in afferent renal nerve activity (ARNA) and release of substance P (SP) and calcitonin gene-related peptide (CGRP) from the renal pelvis are suppressed in Dahl salt-sensitive (DS), but not -resistant (DR), rats fed a high-salt (HS) diet.

Methods and results: Male DS and DR rats were given a HS or low-salt (LS) diet for 3 weeks. Perfusion of capsaicin (CAP, 10(-6)M), a selective TRPV1 agonist, into the left renal pelvis increased ipsilateral ARNA in all groups, but with a smaller magnitude in DS-HS compared to other groups. CAP increased contralateral urine flow in all groups except DS-HS rats. CAP-induced release of SP and CGRP from the renal pelvis was less in DS-HS compared to other groups. Western blot showed that TRPV1 expression in the kidney decreased while expression of neurokinin 1 receptors increased in DS-HS compared to other groups.

Conclusion: TRPV1-mediated increases in ARNA and release of SP and CGRP in the renal pelvis are impaired in DS rats fed a HS diet, which can likely be attributed to suppressed TRPV1 expression in the kidney and contributes to increased salt sensitivity.

Fig. 1

MAP from DR-LS, DR-HS, DS-LS, DS-HS and DOCA-salt rats (n = 7–8 in each group). * p < 0.05 compared with DR-LS, DS-LS and DR-HS groups; ^# p < 0.05 compared with DS-HS group.

Fig. 2

ARNA activated by CAP perfused into the left renal pelvis in DR-LS, DR-HS, DS-LS, DS-HS and DOCA-salt groups (n = 5–6 in each group). ** p < 0.01 compared with basal value of each group.

Fig. 3

CAP-induced ipsilateral ARNA in DR-LS, DR-HS, DS-LS, DS-HS and DOCA-salt rats (n = 5–6 in each group). ** p < 0.01 compared with DR-LS, DR-HS, DS-LS and DOCA-salt groups.

Fig. 4

CAP-induced contralateral urine flow in DR-LS, DR-HS, DS-LS and DS-HS rats (n = 5–6 in each group). * p < 0.05 compared with DR-LS, DR-HS and DS-LS groups; ^# p < 0.05 compared with the DS-HS group.

Fig. 5

CAP-triggered SP release from incubated renal pelvis in DR-LS, DR-HS, DS-LS, DS-HS and DOCA-salt rats (n = 5–6 in each group). * p < 0.05 compared with respective basal value; ** p < 0.01 compared with respective basal value; ^# p < 0.05 compared with DR-LS, DR-HS, DS-LS and DOCA-salt groups.

Fig. 6

CAP-triggered CGRP release from incubated renal pelvis in DR-LS, DR-HS, DS-LS, DS-HS and DOCA-salt rats (n = 5–6 in each group). * p < 0.05 compared with respective basal value; ** p < 0.01 compared with respective basal value; ^# p < 0.05 compared with DR-LS, DR-HS, DS-LS and DOCA-salt groups.