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(Hypertension. 2005;46:992.)
© 2005 American Heart Association, Inc.

Part 2 Original Articles

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

From Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, Mich.

Correspondence to Donna H. Wang, MD, Department of Medicine, College of Human Medicine, Michigan State University, B316 Clinical Center, East Lansing, MI 48824. E-mail donna.wang{at}ht.msu.edu

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 (68.9±2.8 pg/mL) perfusion into the renal pelvis was prevented either by capsazepine (22.5±10.1 pg/mL) given ipsilaterally into the renal pelvis or by ipsilateral renal denervation (25.9±2.3 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 • diuresis • sensory nerves • vanilloid receptor 1 • capsaicin • renal pelvis

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