Renal Inflammation in DOCA-Salt hypertension: Role of renal nerves and arterial pressure

Christopher T Banek, Madeline M. Gauthier, Dusty A. Van Helden, Gregory D. Fink, John W Osborn Jr

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Recent reports indicate that, in addition to treating hypertension, renal denervation (RDN) also mitigates renal inflammation. However, because RDN decreases renal perfusion pressure, it is unclear whether these effects are because of the direct effects of RDN on inflammatory signaling or secondary to decreased arterial pressure (AP). Therefore, this study was conducted to elucidate the contribution of renal nerves to renal inflammation in the deoxycorticosterone (DOCA)-salt rat, a model in which RDN decreases AP and abolishes renal inflammation. In Experiment 1, we assessed the temporal changes in renal inflammation by measuring renal cytokines and AP in DOCA-salt rats. Uninephrectomized (1K) adult male Sprague Dawley rats that received surgical RDN or sham (Sham) were administered DOCA (100 mg, SC) and 0.9% saline for 21 days. AP was measured by radiotelemetry, and urinary cytokine excretion was measured repeatedly. In Experiment 2, the contribution of renal nerves in renal inflammation was assessed in a 2-kidney DOCA-salt rat to control for renal perfusion pressure. DOCA-salt treatment was administered after unilateral (U-)RDN. In Experiment 1, DOCA-salt-induced increases in AP and renal inflammation (assessed by urinary cytokines) were attenuated by RDN versus Sham. In Experiment 2, GRO/KC (growth-related oncogene/keratinocyte chemoattractant), MCP (monocyte chemoattractant protein)-1, and macrophage infiltration were lower in the denervated kidney versus the contralateral Sham kidney. No differences in T-cell infiltration were observed. Together, these data support the hypothesis that renal nerves mediate, in part, the development of renal inflammation in the DOCA-salt rat independent of hypertension. The mechanisms and cell-specificity mediating these effects require further investigation.

Original languageEnglish (US)
Pages (from-to)1079-1086
Number of pages8
JournalHypertension
Volume73
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Desoxycorticosterone Acetate
Renal Hypertension
Arterial Pressure
Salts
Inflammation
Kidney
Denervation
Cytokines
Perfusion

Keywords

  • cardiovascular disease
  • cytokines
  • denervation
  • hypertension
  • inflammation

Cite this

Renal Inflammation in DOCA-Salt hypertension : Role of renal nerves and arterial pressure. / Banek, Christopher T; Gauthier, Madeline M.; Van Helden, Dusty A.; Fink, Gregory D.; Osborn Jr, John W.

In: Hypertension, Vol. 73, No. 5, 01.05.2019, p. 1079-1086.

Research output: Contribution to journalArticle

Banek, Christopher T ; Gauthier, Madeline M. ; Van Helden, Dusty A. ; Fink, Gregory D. ; Osborn Jr, John W. / Renal Inflammation in DOCA-Salt hypertension : Role of renal nerves and arterial pressure. In: Hypertension. 2019 ; Vol. 73, No. 5. pp. 1079-1086.
@article{91c79d0852e24cce859def2f44a20d9d,
title = "Renal Inflammation in DOCA-Salt hypertension: Role of renal nerves and arterial pressure",
abstract = "Recent reports indicate that, in addition to treating hypertension, renal denervation (RDN) also mitigates renal inflammation. However, because RDN decreases renal perfusion pressure, it is unclear whether these effects are because of the direct effects of RDN on inflammatory signaling or secondary to decreased arterial pressure (AP). Therefore, this study was conducted to elucidate the contribution of renal nerves to renal inflammation in the deoxycorticosterone (DOCA)-salt rat, a model in which RDN decreases AP and abolishes renal inflammation. In Experiment 1, we assessed the temporal changes in renal inflammation by measuring renal cytokines and AP in DOCA-salt rats. Uninephrectomized (1K) adult male Sprague Dawley rats that received surgical RDN or sham (Sham) were administered DOCA (100 mg, SC) and 0.9{\%} saline for 21 days. AP was measured by radiotelemetry, and urinary cytokine excretion was measured repeatedly. In Experiment 2, the contribution of renal nerves in renal inflammation was assessed in a 2-kidney DOCA-salt rat to control for renal perfusion pressure. DOCA-salt treatment was administered after unilateral (U-)RDN. In Experiment 1, DOCA-salt-induced increases in AP and renal inflammation (assessed by urinary cytokines) were attenuated by RDN versus Sham. In Experiment 2, GRO/KC (growth-related oncogene/keratinocyte chemoattractant), MCP (monocyte chemoattractant protein)-1, and macrophage infiltration were lower in the denervated kidney versus the contralateral Sham kidney. No differences in T-cell infiltration were observed. Together, these data support the hypothesis that renal nerves mediate, in part, the development of renal inflammation in the DOCA-salt rat independent of hypertension. The mechanisms and cell-specificity mediating these effects require further investigation.",
keywords = "cardiovascular disease, cytokines, denervation, hypertension, inflammation",
author = "Banek, {Christopher T} and Gauthier, {Madeline M.} and {Van Helden}, {Dusty A.} and Fink, {Gregory D.} and {Osborn Jr}, {John W}",
year = "2019",
month = "5",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.119.12762",
language = "English (US)",
volume = "73",
pages = "1079--1086",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Renal Inflammation in DOCA-Salt hypertension

T2 - Role of renal nerves and arterial pressure

AU - Banek, Christopher T

AU - Gauthier, Madeline M.

AU - Van Helden, Dusty A.

AU - Fink, Gregory D.

AU - Osborn Jr, John W

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Recent reports indicate that, in addition to treating hypertension, renal denervation (RDN) also mitigates renal inflammation. However, because RDN decreases renal perfusion pressure, it is unclear whether these effects are because of the direct effects of RDN on inflammatory signaling or secondary to decreased arterial pressure (AP). Therefore, this study was conducted to elucidate the contribution of renal nerves to renal inflammation in the deoxycorticosterone (DOCA)-salt rat, a model in which RDN decreases AP and abolishes renal inflammation. In Experiment 1, we assessed the temporal changes in renal inflammation by measuring renal cytokines and AP in DOCA-salt rats. Uninephrectomized (1K) adult male Sprague Dawley rats that received surgical RDN or sham (Sham) were administered DOCA (100 mg, SC) and 0.9% saline for 21 days. AP was measured by radiotelemetry, and urinary cytokine excretion was measured repeatedly. In Experiment 2, the contribution of renal nerves in renal inflammation was assessed in a 2-kidney DOCA-salt rat to control for renal perfusion pressure. DOCA-salt treatment was administered after unilateral (U-)RDN. In Experiment 1, DOCA-salt-induced increases in AP and renal inflammation (assessed by urinary cytokines) were attenuated by RDN versus Sham. In Experiment 2, GRO/KC (growth-related oncogene/keratinocyte chemoattractant), MCP (monocyte chemoattractant protein)-1, and macrophage infiltration were lower in the denervated kidney versus the contralateral Sham kidney. No differences in T-cell infiltration were observed. Together, these data support the hypothesis that renal nerves mediate, in part, the development of renal inflammation in the DOCA-salt rat independent of hypertension. The mechanisms and cell-specificity mediating these effects require further investigation.

AB - Recent reports indicate that, in addition to treating hypertension, renal denervation (RDN) also mitigates renal inflammation. However, because RDN decreases renal perfusion pressure, it is unclear whether these effects are because of the direct effects of RDN on inflammatory signaling or secondary to decreased arterial pressure (AP). Therefore, this study was conducted to elucidate the contribution of renal nerves to renal inflammation in the deoxycorticosterone (DOCA)-salt rat, a model in which RDN decreases AP and abolishes renal inflammation. In Experiment 1, we assessed the temporal changes in renal inflammation by measuring renal cytokines and AP in DOCA-salt rats. Uninephrectomized (1K) adult male Sprague Dawley rats that received surgical RDN or sham (Sham) were administered DOCA (100 mg, SC) and 0.9% saline for 21 days. AP was measured by radiotelemetry, and urinary cytokine excretion was measured repeatedly. In Experiment 2, the contribution of renal nerves in renal inflammation was assessed in a 2-kidney DOCA-salt rat to control for renal perfusion pressure. DOCA-salt treatment was administered after unilateral (U-)RDN. In Experiment 1, DOCA-salt-induced increases in AP and renal inflammation (assessed by urinary cytokines) were attenuated by RDN versus Sham. In Experiment 2, GRO/KC (growth-related oncogene/keratinocyte chemoattractant), MCP (monocyte chemoattractant protein)-1, and macrophage infiltration were lower in the denervated kidney versus the contralateral Sham kidney. No differences in T-cell infiltration were observed. Together, these data support the hypothesis that renal nerves mediate, in part, the development of renal inflammation in the DOCA-salt rat independent of hypertension. The mechanisms and cell-specificity mediating these effects require further investigation.

KW - cardiovascular disease

KW - cytokines

KW - denervation

KW - hypertension

KW - inflammation

UR - http://www.scopus.com/inward/record.url?scp=85064725479&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064725479&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.119.12762

DO - 10.1161/HYPERTENSIONAHA.119.12762

M3 - Article

C2 - 30879356

AN - SCOPUS:85064725479

VL - 73

SP - 1079

EP - 1086

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 5

ER -