Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension

Christopher T. Banek, Mark M. Knuepfer, Jason D. Foss, Jessica K. Fiege, Ninitha Asirvatham-Jeyaraj, Dusty Van Helden, Yoji Shimizu, John W. Osborn

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension.

Original languageEnglish (US)
Pages (from-to)1415-1423
Number of pages9
JournalHypertension
Volume68
Issue number6
DOIs
StatePublished - Dec 1 2016

Fingerprint

Desoxycorticosterone
Acetates
Salts
Hypertension
Inflammation
Kidney
Cytokines
Renal Hypertension
Sympathectomy
Clinical Protocols
Chemokines
Sprague Dawley Rats
Arterial Pressure
Heart Rate

Keywords

  • afferent neurons
  • arterial pressure
  • denervation
  • deoxycorticosterone acetate
  • hypertension
  • inflammation

Cite this

Resting Afferent Renal Nerve Discharge and Renal Inflammation : Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension. / Banek, Christopher T.; Knuepfer, Mark M.; Foss, Jason D.; Fiege, Jessica K.; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W.

In: Hypertension, Vol. 68, No. 6, 01.12.2016, p. 1415-1423.

Research output: Contribution to journalArticle

Banek, Christopher T. ; Knuepfer, Mark M. ; Foss, Jason D. ; Fiege, Jessica K. ; Asirvatham-Jeyaraj, Ninitha ; Van Helden, Dusty ; Shimizu, Yoji ; Osborn, John W. / Resting Afferent Renal Nerve Discharge and Renal Inflammation : Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension. In: Hypertension. 2016 ; Vol. 68, No. 6. pp. 1415-1423.
@article{4f4d886ef3844d2783ebaa29d4dce55f,
title = "Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension",
abstract = "Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9{\%} saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 {\%}Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50{\%} in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension.",
keywords = "afferent neurons, arterial pressure, denervation, deoxycorticosterone acetate, hypertension, inflammation",
author = "Banek, {Christopher T.} and Knuepfer, {Mark M.} and Foss, {Jason D.} and Fiege, {Jessica K.} and Ninitha Asirvatham-Jeyaraj and {Van Helden}, Dusty and Yoji Shimizu and Osborn, {John W.}",
year = "2016",
month = "12",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.116.07850",
language = "English (US)",
volume = "68",
pages = "1415--1423",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Resting Afferent Renal Nerve Discharge and Renal Inflammation

T2 - Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension

AU - Banek, Christopher T.

AU - Knuepfer, Mark M.

AU - Foss, Jason D.

AU - Fiege, Jessica K.

AU - Asirvatham-Jeyaraj, Ninitha

AU - Van Helden, Dusty

AU - Shimizu, Yoji

AU - Osborn, John W.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension.

AB - Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension.

KW - afferent neurons

KW - arterial pressure

KW - denervation

KW - deoxycorticosterone acetate

KW - hypertension

KW - inflammation

UR - http://www.scopus.com/inward/record.url?scp=84994817754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994817754&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.116.07850

DO - 10.1161/HYPERTENSIONAHA.116.07850

M3 - Article

C2 - 27698066

AN - SCOPUS:84994817754

VL - 68

SP - 1415

EP - 1423

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 6

ER -