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Segmental regulation of sodium and water excretion by TRPV1 activation in the kidney Zhu Y; Wang DHJ Cardiovasc Pharmacol 2008[May]; 51 (5): 437-42Our 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 (microL.ming; 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 (micromol.ming; 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) 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 |Animals[MESH]|Blood Pressure/drug effects[MESH]|Body Water/*metabolism[MESH]|Capsaicin/analogs & derivatives/pharmacology[MESH]|Cations, Monovalent[MESH]|Creatinine/blood/urine[MESH]|Glomerular Filtration Rate[MESH]|Kidney/*drug effects/innervation/metabolism[MESH]|Lithium Chloride/pharmacology[MESH]|Lithium/blood/urine[MESH]|Male[MESH]|Natriuresis/drug effects/physiology[MESH]|Nerve Fibers/metabolism[MESH]|Rats[MESH]|Rats, Wistar[MESH]|Renal Circulation/drug effects[MESH]|Sodium/blood/*urine[MESH]|TRPV Cation Channels/*agonists/antagonists & inhibitors/*metabolism[MESH] |
