TRPV1‐mediated diuresis and natriuresis induced by hypertonic saline perfusion of renal pelvis

Abstract

To test the hypothesis that the transient receptor potential vanilloid type 1 (TRPVl) channels expressed in sensory nerves innervating the renal pelvis mediate diuresis and natriuresis induced by hypertonic saline perfusion, sodium chloride at 150, 300 and 600 mM was perfused into the left renal pelvis (LRP) of anesthetized rats at a rate without changing renal perfusion pressure. Mean arterial pressure was not altered by LRP perfusion of NaCl at any of these concentrations. LRP perfusion of NaCl at 600 mM (equal to 1200 mOsm/L) but not 150 or 300 mM significantly increased urine flow rate (Uflow) and urinary sodium excretion (UNa) in the contralateral kidney. The increases in Uflow and UNa in the contralateral kidney were blocked by a selective TRPVl antagonist, capsazepine (CAPZ), or a selective substance P (SP) receptor antagonist, RP67580, given LRP, or by ipsilateral renal denervation. In contrast, LRP perfusion of mannitol at 1200 mOsm/L had no effect on Uflow and UNa in the contralateral kidney. Incubation of the renal pelvis in vitro with NaCl at 600 mM but not mannitol significantly increased SP release, which was blocked by CAPZ and RP67580. Taken together, our data indicate that hypertonic NaCl perfusion into LRP leads to contralateral diuresis and natriuresis via renorenal reflex by activation of TRPV1 and SP receptors expressed in sensory nerves innervating the ipsilateral renal pelvis, a mechanism that may be critically involved in sodium and water homeostasis.