Diuresis and Natriuresis Caused by Activation of VR1-Positive Sensory Nerves in Renal Pelvis of Rats

Abstract

Abstract-To test the hypothesis that activation of the vanilloid receptor 1 (VR1) expressed in sensory nerves innervating the renal pelvis leads to diuresis and natriuresis, a selective VR1 receptor agonist, capsaicin (2.4 nmol), or vehicle was perfused intravenously or into the left renal pelvis of anesthetized rats at a rate without changing renal perfusion pressure. Mean arterial pressure was not altered by capsaicin administered intravenously or into the renal pelvis. Capsaicin perfusion into the left renal pelvis but not intravenously caused significant increases in urine flow rate and urinary sodium excretion bilaterally in a dose-dependent manner, which were abolished by capsazepine, a selective VR1 receptor antagonist, given ipsilaterally to the renal pelvis or by ipsilateral renal denervation. Capsaicin given intravenously or into the left renal pelvis increased plasma calcitonin gene-related peptide levels to the same extent. Increased plasma calcitonin gene-related peptide levels induced by capsaicin (68.9Ϯ2.8 pg/mL) perfusion into the renal pelvis was prevented either by capsazepine (22.5Ϯ10.1 pg/mL) given ipsilaterally into the renal pelvis or by ipsilateral renal denervation (25.9Ϯ2.3 pg/mL). Taken together, our data show that unilateral activation of VR1-positive sensory nerves innervating the renal pelvis leads to bilateral diuresis and natriuresis via a mechanism that is independent of plasma calcitonin gene-related peptide levels. These data suggest that VR1-positive sensory nerves in the kidney enhance renal excretory function, a mechanism that may be critically involved in sodium and fluid homeostasis. Key Words: natriuresis Ⅲ diuresis Ⅲ sensory nerves Ⅲ vanilloid receptor 1 Ⅲ capsaicin Ⅲ renal pelvis T he renal pelvis is heavily innervated by primary sensory afferent nerves with their nerve terminals distributing in mucous and in proximity to the epithelial cells. 1 The renal pelvis therefore is considered as a sensory organ sensing mechano-stimuli and chemo-stimuli leading to altered renal excretory function such as diuresis and natriuresis. 2,3 Previous studies have shown that ipsilateral obstruction to urine flow or elevation of pressure in the renal pelvis activates renal mechano-sensitive neurons, which results in an increase in ipsilateral afferent renal nerve activity (ARNA). 2,4 Increased ipsilateral ARNA subsequently induces a contralateral diuresis and natriuresis via an inhibition on contralateral efferent renal nerve activity, which is known as the renorenal reflex. 2,4 The vanilloid receptor (VR1), also known as the capsaicin receptor or a member of the transient receptor potential vanilloid subfamily, was cloned by the use of the "hot" pepper-derived vanilloid compound, capsaicin, as a ligand. 5 The VR1 receptor, a ligand gate ion channel, is mainly expressed in a subpopulation of primary sensory afferents and functions to integrate multiple stimuli including proton, heat, and vanilloid compounds such as capsacin. 6 -7 VR1-positive sensory nerves have been implicated to play an...

Tonic Postganglionic Sympathetic Inhibition Induced by Afferent Renal Nerves?

“…The influence of afferent renal nerve fibers via an NK 1 -dependant mechanism on sympathetic drive to other sites than the kidneys seems to be limited: intrarenal stimulation of TRPV1 receptors with capsaicin produced a very long-lasting highly significant renal sympathodepression but had no significant influence on blood pressure or heart rate, although the very same doses of capsaicin had no significant effect on blood pressure, heart rate, or RSNA at all when administered intravenously. Because TRPV1 receptors are only localized on peptidergic afferent nerves [22][23][24] and also on nerve fibers within the kidney, 18,25,26 the effect must be initiated by these very nerve fibers.…”

Interdependent Regulation of Afferent Renal Nerve Activity and Renal Function: Role of Transient Receptor Potential Vanilloid Type 1, Neurokinin 1, and Calcitonin Gene-Related Peptide Receptors

“…Our previous data show that activation of TRPV1 by CAP perfused into the unilateral renal pelvis leads to bilateral diuresis and natriuresis via a dual renorenal reflex and that this effect is abolished after ipsilateral renal denervation (Zhu et al, 2005). Moreover, hypertonic saline perfused into the renal pelvis causes increases in ipsilateral afferent renal nerve activity (ARNA) and contralateral renal excretory function by activation of TRPV1 and neurokinin 1 (NK1) receptors (Zhu et al, 2007).…”

“…0.18/o.d. 0.22 mm; BASi, West Lafayette, IN) was placed inside the PE-50 catheter with its tip extending 1 to 2 mm out of the PE-50 catheter for perfusion drugs at 20 l ⅐ min Ϫ1 , a rate that did not change renal pelvis pressure (Zhu et al, 2005(Zhu et al, , 2007.…”

“…The rats were stabilized for 1.5 h before the experiment started. The drugs were perfused into the renal pelvis in two 3-min periods; i.e., capsazepine (CAPZ, 0.4 mM; Calbiochem, San Diego, CA) (Zhu et al, 2005), an antagonist of TRPV1; RP67580 (0.2 mM; Tocris Cookson Inc., Ellisville, MO) (Zhu et al, 2005) and L703,606 (10 M; Sigma-Aldrich, St. Louis, MO), antagonists of NK1 receptors; or CGRP8-37 (0.32 M; American Peptide Co., Inc., Sunnyvale, CA), an antagonist of CGRP receptors, were perfused within the 1st 3-min period, as well as CAP, SP, or CGRP (0.13 M; Sigma-Aldrich) with or without the antagonists within the 2nd 3-min period following right after the 1st 3-min period. In the case when one of the drugs above was perfused alone (either agonists or antagonists alone), the other period was perfused with the vehicle.…”

“…Urine flow rate (Uflow) and urinary sodium excretion (UNa) were determined in the samples collected from the contralateral kidney. Urinary sodium excretion was measured as described previously using a flame photometer (Model IL 943; Instrumentation Laboratory, Lexington, MA), and Uflow and UNa were expressed per gram of kidney weight per minute (micromole/minute/ gram) (Zhu et al, 2005(Zhu et al, , 2007.…”