title: Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin.
abstract: 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 PGE(2) 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 PGE(2) 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 PGE(2) 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 PGE(2) 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 PGE(2) 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.
authors.affiliation: Department of Internal Medicine, Department of Veterans Affairs Medical Center and University of Iowa Carver College of Medicine, Iowa City, Iowa 52246, USA. ulla-kopp@uiowa.edu
authors.forename: Ulla C
authors.initials: UC
authors.lastname: Kopp
authors.forename: Olaf
authors.initials: O
authors.lastname: Grisk
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Cicha
authors.forename: Lori A
authors.initials: LA
authors.lastname: Smith
authors.forename: Antje
authors.initials: A
authors.lastname: Steinbach
authors.forename: Torsten
authors.initials: T
authors.lastname: Schlüter
authors.forename: Nicole
authors.initials: N
authors.lastname: Mähler
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000294:innervation / Q000502:physiology*; D007682:Kidney Pelvis / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012982:Sodium, Dietary / Q000494:pharmacology* / Q000652:urine; D013373:Substance P / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012982:Sodium, Dietary; D013373:Substance P; C086539:BQ 788; D015232:Dinoprostone; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D009638:Norepinephrine