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Am J Physiol Regul Integr Comp Physiol 297: R337-R351, 2009. First published May 27, 2009; doi:10.1152/ajpregu.91029.2008
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ARTICLES

Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin

Ulla C. Kopp,1 Olaf Grisk,2 Michael Z. Cicha,1 Lori A. Smith,1 Antje Steinbach,2 Torsten Schlüter,2 Nicole Mähler,2 and Tomas Hökfelt3

1Departments of Internal Medicine and Pharmacology, Department of Veterans Affairs Medical Center and University of Iowa Carver College of Medicine, Iowa City, Iowa; 2Department of Physiology, University of Greifswald, Karlsburg, Germany; and 3Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

Submitted 18 December 2008 ; accepted in final form 25 May 2009

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which in turn decreases ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. We now examined whether the ERSNA-induced increases in ARNA are modulated by dietary sodium and the role of endothelin (ET). The ARNA response to reflex increases in ERSNA was enhanced in high (HNa)- vs. low-sodium (LNa) diet rats, 7,560 ± 1,470 vs. 900 ± 390%·s. The norepinephrine (NE) concentration required to increase PGE2 and substance P release from isolated renal pelvises was 10 pM in HNa and 6,250 pM in LNa diet rats. In HNa diet pelvises 10 pM NE increased PGE2 release from 67 ± 6 to 150 ± 13 pg/min and substance P release from 6.7 ± 0.8 to 12.3 ± 1.8 pg/min. In LNa diet pelvises 6,250 pM NE increased PGE2 release from 64 ± 5 to 129 ± 22 pg/min and substance P release from 4.5 ± 0.4 to 6.6 ± 0.7 pg/min. In the renal pelvic wall, ETB-R are present on unmyelinated Schwann cells close to the afferent nerves and ETA-R on smooth muscle cells. ETA-receptor (R) protein expression in the renal pelvic wall is increased in LNa diet. In HNa diet, renal pelvic administration of the ETB-R antagonist BQ788 reduced ERSNA-induced increases in ARNA and NE-induced release of PGE2 and substance P. In LNa diet, the ETA-R antagonist BQ123 enhanced ERSNA-induced increases in ARNA and NE-induced release of substance P without altering PGE2 release. In conclusion, activation of ETB-R and ETA-R contributes to the enhanced and suppressed interaction between ERSNA and ARNA in conditions of HNa and LNa diet, respectively, suggesting a role for ET in the renal control of ERSNA that is dependent on dietary sodium.

sensory nerves; substance P; PGE2; endothelin A receptors; endothelin B receptors; renal pelvis; norepinephrine



Address for reprint requests and other correspondence: U. C. Kopp, Dept. of Internal Medicine, Veterans Affairs Medical Center, Bldg. 41, Rm. 124, Highway 6W, Iowa City, IA 52246 (e-mail: ulla-kopp{at}uiowa.edu)







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