Segmental regulation of sodium and water excretion by TRPV1 activation in the kidney

Our previous studies show that activation of the transient receptor potential vanilloid type 1 (TRPV1) channels by a selective agonist, capsaicin (CAP), given unilaterally into the renal pelvis leads to increases in urine flow rate (Uflow) and urinary sodium excretion (UNa) bilaterally, although the mechanisms underlying enhanced renal excretory function are unknown. The present study was designed to determine the contribution of each of the renal segments to enhanced renal excretory function when TRPV1 expressed in sensory nerve fibers innervating the renal pelvis is activated. To accomplish the goal, LiCl was given intravenously to male Wistar rats while the left renal pelvis (LRP) was perfused with vehicle or CAP with or without a selective TRPV1 antagonist, capsazepine (CAPZ). Uflow and clearance of creatinine, lithium, sodium, and water, either filtered or fractionally, were determined in both kidneys. LRP perfusion of CAP at 2.4 nmol increased Uflow (mu L.min(-1)g(-1); ipsilaterally from 6.6 +/- 0.6 to 14.6 +/- 2.2 and contralaterally from 7.4 +/- 0.7 to 13.9 +/- 1.8, P < 0.05) and UNa (mu mol.min(-1)g(-1); ipsilaterally from 0.6 +/- 0.2 to 1.8 +/- 0.3 and contralaterally from 0.7 +/- 0.2 to 1.9 +/- 0.4, P < 0.05). Ipsilateral blockade of the TRPV1 with CAPZ at 24 nmol prevented CAP-induced increases in Uflow and UNa bilaterally. Creatinine, lithium, sodium, and free water clearance (ml.min(-1)) were increased in CAP (1.47 +/- 0.27, 0.44 +/- 0.05, 0.026 +/- 0.004, 0.41 +/- 0.05, respectively) compared to vehicle (0.72 +/- 0.12, 0.25 +/- 0.05, 0.010 +/- 0.001, 0.24 +/- 0.05), CAPZ+ CAP (0.83 +/- 0.13, 0.24 +/- 0.03, 0.014 +/- 0.002, 0.23 +/- 0.03), and CAPZ (0.88 +/- 0.05, 0.21 +/- 0.01, 0.010 +/- 0.001, 0.20 +/- 0.01) groups (P : 0.01). Filtered sodium load, distal delivery of sodium, and distal sodium reabsorption (mu Eq.min(-1)) were also increased in CAP (202.2 +/- 33.3, 61.3 +/- 7.4, 57.6 +/- 7.4, respectively) compared to vehicle (97.7 +/- 16.6, 33.6 +/- 5.8, 32.2 +/- 5.9), CAPZ+CAP (110.5 +/- 16.3, 32.5 +/- 4.5, 30.7 +/- 4.3), and CAPZ (118.0 +/- 4.5, 27.9 +/- 1.2, 26.8 +/- 1.2) groups (P <= 0.01). In contrast, fractional lithium and sodium excretion, absolute proximal reabsorption, fractional proximal reabsorption, fractional distal sodium, and water reabsorption were not different among groups. Therefore, activation of the TRPV1 expressed in primary afferent nerves innervating the renal pelvis leads to diuresis and natriuresis in both kidneys. The TRPV1-induced sodium and water excretion appears to be mediated by increases in glomerular filtration rate and distal tubular delivery of sodium but not by suppression of renal proximal and distal tubular reabsorption, suggesting a key role of segmental regulation of renal function by TRPV1-positive primary sensory nerves in the maintenance of sodium and water homeostasis.