title: Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α2-adrenoceptors on renal sensory nerves.
abstract: Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which then reflexively decreases ERSNA via activation of the renorenal reflexes to maintain low ERSNA. The ERSNA-ARNA interaction is mediated by norepinephrine (NE) that increases and decreases ARNA by activation of renal α(1)-and α(2)-adrenoceptors (AR), respectively. The ERSNA-induced increases in ARNA are suppressed during a low-sodium (2,470 ± 770% s) and enhanced during a high-sodium diet (5,670 ± 1,260% s). We examined the role of α(2)-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of α(2A)-AR and α(2C)-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the α(2)-AR antagonist rauwolscine or the AT1 receptor antagonist losartan alone failed to alter the ARNA responses to reflex increases in ERSNA. Likewise, renal pelvic release of substance P produced by 250 pM NE (from 8.0 ± 1.3 to 8.5 ± 1.6 pg/min) was not affected by rauwolscine or losartan alone. However, rauwolscine+losartan enhanced the ARNA responses to reflex increases in ERSNA (4,680 ± 1,240%·s), and renal pelvic release of substance P by 250 pM NE, from 8.3 ± 0.6 to 14.2 ± 0.8 pg/min. During a high-sodium diet, rauwolscine had no effect on the ARNA response to reflex increases in ERSNA or renal pelvic release of substance P produced by NE. Losartan was not examined because of low endogenous ANG II levels in renal pelvic tissue during a high-sodium diet. Increased activation of α(2)-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of α(2)-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake.
authors.affiliation: Dept. of Internal Medicine, Department of Veterans Affairs Medical Center, Bldg. 41, Highway 6W, Iowa City, IA 52246, USA. ulla-kopp@uiowa.edu
authors.forename: Ulla C
authors.initials: UC
authors.lastname: Kopp
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Cicha
authors.forename: Lori A
authors.initials: LA
authors.lastname: Smith
authors.forename: Saku
authors.initials: S
authors.lastname: Ruohonen
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fritz
authors.forename: Tomas
authors.initials: T
authors.lastname: Hökfelt
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism; D004525:Efferent Pathways / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D007682:Kidney Pelvis / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D012982:Sodium, Dietary / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D018341:Receptors, Adrenergic, alpha-2; D012982:Sodium, Dietary; D013373:Substance P; D015232:Dinoprostone; D009638:Norepinephrine