Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II–Induced Hypertension

Xiao, Liang; Kirabo, Annet; Wu, Jing; Saleh, Mohamed A.; Zhu, Linjue; Wang, Feng; Takahashi, Takamune; Loperena, Roxana; Foss, Jason D.; Mernaugh, Raymond L.; Chen, Wei; Roberts, Jackson; Osborn, John W.; Itani, Hana A.; Harrison, David G.

doi:10.1161/circresaha.115.306010

Cited by 233Renin-Angiotensin System StudiesBlood Pressure and Hypertension StudiesRenal and Vascular Pathologies

Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II–Induced Hypertension

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Xiao, Liang, Kirabo, Annet, Wu, Jing, Saleh, Mohamed A., Zhu, Linjue, Wang, Feng, Takahashi, Takamune, Loperena, Roxana +7 more·2015·Circulation Research

DOI 10.1161/circresaha.115.306010PMC PMC4629828

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Abstract

Rationale: Inflammation and adaptive immunity play a crucial role in the development of hypertension. Angiotensin II and probably other hypertensive stimuli activate the central nervous system and promote T-cell activation and end-organ damage in peripheral tissues. Objective: To determine if renal sympathetic nerves mediate renal inflammation and T-cell activation in hypertension. Methods and Results: Bilateral renal denervation using phenol application to the renal arteries reduced renal norepinephrine levels and blunted angiotensin II–induced hypertension. Bilateral renal denervation also reduced inflammation, as reflected by decreased accumulation of total leukocytes, T cells, and both CD4 + and CD8 + T cells in the kidney. This was associated with a marked reduction in renal fibrosis, albuminuria, and nephrinuria. Unilateral renal denervation, which partly attenuated blood pressure, only reduced inflammation in the denervated kidney, suggesting that this effect is pressure independent. Angiotensin II also increased immunogenic isoketal-protein adducts in renal dendritic cells (DCs) and increased surface expression of costimulation markers and production of interleukin (IL)-1α, IL-1β, and IL-6 from splenic DCs. Norepinephrine also dose dependently stimulated isoketal formation in cultured DCs. Adoptive transfer of splenic DCs from angiotensin II–treated mice primed T-cell activation and hypertension in recipient mice. Renal denervation prevented these effects of hypertension on DCs. In contrast to these beneficial effects of ablating all renal nerves, renal afferent disruption with capsaicin had no effect on blood pressure or renal inflammation. Conclusions: Renal sympathetic nerves contribute to DC activation, subsequent T-cell infiltration and end-organ damage in the kidney in the development of hypertension.

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Multiple preclinical studies show that total renal denervation causes a significant and sustained fall in mean arterial blood pressure.
“Multiple preclinical studies have demonstrated that total RDN (TRDN, defined as ablation of the sympathetic efferent and sensory afferent nerves) causes a significant and sustained reduction in mean arterial blood pressure20,69–73.”
From Renal nerves in physiology, pathophysiology and interoception (2025) · cites this paper as [72]
The Results section reports that bilateral renal denervation blunted angiotensin II–induced hypertension in mice, with lower systolic and diastolic pressures than in sham-operated mice. It also reports lower blood pressure during the two weeks after denervation in a separate mouse protocol. The paper does not report a mean arterial pressure result or establish that multiple preclinical studies found a significant, sustained reduction; its Introduction says some, but not all, animal studies found blood-pressure reductions. (LLM, conf=0.85)
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Abstract 642: Renal Denervation Prevents Dendritic Cell Activation and Renal T Cell Infiltration and Subsequent Renal Damage in Mice with Angiotensin II-induced Hypertension
Xiao, L., Kirabo, A., Wu, J. F., Saleh, M. A., Zhu, L., & Harrison, D. G. (2014) · Hypertension · doi:10.1161/hyp.64.suppl_1.642
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Renal denervation prevents renal T cell activation in mice during angiotensin II‐induced hypertension
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Renal denervation prevents dendritic cell activation and renal T cell activation in mice in angiotensin II‐induced hypertension (1082.4)
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Abstract 60: Renal Denervation Prevents Dendritic Cell Activation and Renal T Cell Activation in Mice During Angiotensin Ii-induced Hypertension
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Abstract P616: Renal Sympathetic Outflow And Beta-adrenergic Signaling Promote Dendritic Cell Activation In Hypertension
Xiao, L., Kirabo, A., Loperena, R., Foss, J. D., Mernaugh, R. L., Roberts, L. J., Itani, H. A., Chen, W., & Harrison, D. G. (2015) · Hypertension · doi:10.1161/hyp.66.suppl_1.p616
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Authors: Xiao, L., Kirabo, A., Wu, J., Saleh, M. A., Zhu, L., Wang, F., Takahashi, T., Loperena, R., Foss, J. D., Mernaugh, R. L., Chen, W., Roberts, J., Osborn, J. W., Itani, H. A., & Harrison, D. G.
Affiliations: University of Minnesota (US)
ORCID: Xiao, Liang
Kirabo, Annet
Wu, Jing
Saleh, Mohamed A.
Wang, Feng
Takahashi, Takamune
Loperena, Roxana
Foss, Jason D.
Chen, Wei
Osborn, John W.
Itani, Hana A.
Harrison, David G.
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2015-08-28
Volume: 117
Issue: 6
Pages: 547-557
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/circresaha.115.306010
PMC: PMC4629828
OpenAlex: W2166852030
Cited by: 233
References: 42
Citations by year: 2026: 11 · 2025: 17 · 2024: 19 · 2023: 18 · 2022: 23 · 2021: 19 · 2020: 30 · 2019: 25 · 2018: 22 · 2017: 23 · 2016: 20 · 2015: 6
FWCI: 17.23
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Vanderbilt University
Vanderbilt University Medical Center
National Heart, Lung, and Blood Institute (R01HL039006, R01HL108701, K01HL130497, P01 HL58000, R01HL116476, F32HL124972, P01HL058000, HL039006, P01HL095070, R01HL105294, R01HL125865)
National Institute of General Medical Sciences (GM015431, P50GM015431, P01GM015431, R25GM062459, T32GM007569)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079341)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal and Vascular Pathologies
Keywords: renal denervation, angiotensin II-induced hypertension, renal inflammation, T cell activation, renal sympathetic nerves, dendritic cells, norepinephrine, renal fibrosis, albuminuria, renal afferent nerves, capsaicin, adaptive immunity, interleukins
MeSH terms: Angiotensin II, Animals, Hypertension, Immunity, Cellular, Kidney, Mice, Inbred C57BL, Random Allocation, Sympathectomy, Mice, Knockout, Mice

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Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II–Induced Hypertension

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