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Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II–Induced Hypertension
Open accessAbstract
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 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]
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Citations
Cites
Nitric oxide synthases: regulation and function
Forstermann, U., & Sessa, W. C. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehr304 · Cited by 4,409
Cellular and Molecular Immunology
Abbas, A. K., Lichtman, A. H., & Pillai, S. S. (1994) · Cited by 3,571
Cellular and Molecular Immunology
Denman, A. M. (1992) · Postgraduate Medical Journal · doi:10.1136/pgmj.68.798.305 · Cited by 2,807
A Controlled Trial of Renal Denervation for Resistant Hypertension
Bhatt, D. L., Kandzari, D. E., O'Neill, W. W., D'Agostino, R., Flack, J. M., Katzen, B. T., Leon, M. B., Liu, M., Mauri, L., Negoita, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1402670 · Cited by 2,186
Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction
Guzik, T. J., Hoch, N. E., Brown, K. A., McCann, L. A., Rahman, A., Dikalov, S., Goronzy, J., Weyand, C., & Harrison, D. G. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070657 · Cited by 1,736
Self-citationInflammation, Immunity, and Hypertension
Harrison, D. G., Guzik, T. J., Lob, H. E., Madhur, M. S., Marvar, P. J., Thabet, S., Vinh, A., & Weyand, C. M. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.163576 · Cited by 893
Self-citationJakubzick, C. V., Gautier, E., Gibbings, S. L., Sojka, D. K., Schlitzer, A., Johnson, T. E., Ivanov, S., Duan, Q., Bala, S., Condon, T., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.007 · Cited by 762
Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension
Symplicity HTN-1 Investigators (2011) · Hypertension · doi:10.1161/hypertensionaha.110.163014 · Cited by 743
Predictors of blood pressure response in the SYMPLICITY HTN-3 trial
Kandzari, D. E., Bhatt, D. L., Brar, S. K., Devireddy, C. M., Esler, M., Fahy, M. P., Flack, J. M., Katzen, B. T., Lea, J. P., Lee, D. P., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu441 · Cited by 552
DC isoketal-modified proteins activate T cells and promote hypertension
Kirabo, A., Fontana, V., de Faria, A. P., Loperena, R., Galindo, C. L., Wu, J., Bikineyeva, A. T., Dikalov, S., Xiao, L., Chen, W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74084 · Cited by 549
Self-citationRenal Sympathetic Denervation for Treatment of Drug-Resistant Hypertension
Esler, M., Krum, H., Schlaich, M. P., Schmieder, R. E., Böhm, M., & Sobotka, P. A. (2012) · Circulation · doi:10.1161/circulationaha.112.130880 · Cited by 462
Translational medicine: the antihypertensive effect of renal denervation
DiBona, G. F., & Esler, M. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00647.2009 · Cited by 432
Kruppel-like Factor 4 Regulates Endothelial Inflammation
Hamik, A., Lin, Z., Kumar, A., Balcells, M., Sinha, S., Katz, J. P., Feinberg, M. W., Gerszten, R. E., Edelman, E. R., & Jain, M. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700078200 · Cited by 391
Kohm, A. P., & Sanders, V. M. (2001) · PubMed · Cited by 357
Marvar, P. J., Thabet, S., Guzik, T. J., Lob, H. E., McCann, L. A., Weyand, C., Gordon, F. J., & Harrison, D. G. (2010) · Circulation Research · doi:10.1161/circresaha.110.217299 · Cited by 319
Self-citationVinh, A., Chen, W., Blinder, Y., Weiss, D., Taylor, W. R., Goronzy, J. J., Weyand, C. M., Harrison, D. G., & Guzik, T. J. (2010) · Circulation · doi:10.1161/circulationaha.109.930446 · Cited by 305
Self-citationLymphocyte responses exacerbate angiotensin II-dependent hypertension
Crowley, S. D., Song, Y.-S., Lin, E. E., Griffiths, R., Kim, H., & Ruiz, P. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00373.2009 · Cited by 258
Oligoclonal CD8 + T Cells Play a Critical Role in the Development of Hypertension
Trott, D. W., Thabet, S., Kirabo, A., Saleh, M. A., Itani, H. A., Norlander, A. E., Wu, J., Goldstein, A. E., Arendshorst, W. J., Madhur, M. S., et al. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.04147 · Cited by 253
Self-citationWu, J., Thabet, S., Kirabo, A., Trott, D. W., Saleh, M. A., Xiao, L., Madhur, M. S., Chen, W., & Harrison, D. G. (2013) · Circulation Research · doi:10.1161/circresaha.114.302157 · Cited by 244
Self-citationKamat, N. V., Thabet, S., Xiao, L., Saleh, M. A., Kirabo, A., Madhur, M. S., Delpire, E. J., Harrison, D. G., & McDonough, A. A. (2015) · Hypertension · doi:10.1161/hypertensionaha.114.04975 · Cited by 212
Self-citationBöhm, M., Mahfoud, F., Ukena, C., Hoppe, U. C., Narkiewicz, K., Negoita, M., Ruilope, L. M., Schlaich, M. P., Schmieder, R. E., Whitbourn, R., et al. (2015) · Hypertension · doi:10.1161/hypertensionaha.114.05010 · Cited by 190
Pulsatile Stretch Stimulates Superoxide Production in Human Aortic Endothelial Cells
Hishikawa, K., & Lüscher, T. F. (1997) · Circulation · doi:10.1161/01.cir.96.10.3610 · Cited by 183
Mattson, D. L., Lund, H., Guo, C., Rudemiller, N. P., Geurts, A. M., & Jacob, H. J. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00304.2012 · Cited by 181
Lob, H. E., Marvar, P. J., Guzik, T. J., Sharma, S., McCann, L. A., Weyand, C. M., Gordon, F. J., & Harrison, D. G. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.142646 · Cited by 177
Self-citationYe, S., Ozgur, B. M., & Campese, V. M. (1997) · Kidney International · doi:10.1038/ki.1997.103 · Cited by 167
Role of the NADPH Oxidases in the Subfornical Organ in Angiotensin II–Induced Hypertension
Lob, H. E., Schultz, D. W., Marvar, P. J., Davisson, R. L., & Harrison, D. G. (2012) · Hypertension · doi:10.1161/hypertensionaha.111.00546 · Cited by 109
Self-citationGanta, C. K., Lü, N., Helwig, B. G., Blecha, F., Ganta, R. R., Zheng, L., Ross, C. R., Musch, T. I., Fels, R. J., & Kenney, M. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00125.2005 · Cited by 106
A Limited Renal Injury May Cause a Permanent Form of Neurogenic Hypertension
Ye, S., Gamburd, M., Mozayeni, P., Koss, M., & Campese, V. M. (1998) · American Journal of Hypertension · doi:10.1016/s0895-7061(98)00030-2 · Cited by 106
Pro-inflammatory responses in human monocytes are β1-adrenergic receptor subtype dependent
Grisanti, L. A., Evanson, J., Marchus, E., Jorissen, H., Woster, A. P., DeKrey, W. L., Sauter, E. R., Combs, C. K., & Porter, J. E. (2010) · Molecular Immunology · doi:10.1016/j.molimm.2009.12.013 · Cited by 101
Persu, A., Renkin, J. P., Thijs, L., & Staessen, J. A. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.195263 · Cited by 88
Cyclosporine A-induced hypertension involves synapsin in renal sensory nerve endings
Zhang, W., Li, J.-L., Hosaka, M., Janz, R., Shelton, J. M., Albright, G. M., Richardson, J. A., Südhof, T. C., & Victor, R. G. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.170160397 · Cited by 84
Satou, R., Miyata, K., González-Villalobos, R. A., Ingelfinger, J. R., Navar, L. G., & Kobori, H. (2012) · The FASEB Journal · doi:10.1096/fj.11-195198 · Cited by 74
High Pressure Promotes Monocyte Adhesion to the Vascular Wall
Riou, S., Mees, B., Esposito, B., Merval, R., Vilar, J., Stengel, D., Ninio, E., van Haperen, R., de Crom, R., Tedgui, A., et al. (2007) · Circulation Research · doi:10.1161/01.res.0000265231.59354.2c · Cited by 60
Renal Denervation after Symplicity HTN-3: An Update
Persu, A., Jin, Y., Elmula, F. E. M. F., Jacobs, L., Renkin, J. P., & Kjeldsen, S. E. (2014) · Current Hypertension Reports · doi:10.1007/s11906-014-0460-x · Cited by 39
Mathis, K. W., Venegas‐Pont, M., Flynn, E. R., Williams, J. M., Maric‐Bilkan, C., Dwyer, T. M., & Ryan, M. J. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00602.2012 · Cited by 38
Renal denervation—implications for chronic kidney disease
Veelken, R. A., & Schmieder, R. E. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.59 · Cited by 36
Development of Hypertension Induced by Subpressor Infusion of Angiotensin II
Wu, W. K., Zhang, Y., Ballew, J. R., Fink, G. D., & Wang, D. H. (2000) · Hypertension · doi:10.1161/01.hyp.36.4.549 · Cited by 26
Wang, H., Wang, J., Guo, C., Luo, W., Kleiman, K., & Eitzman, D. T. (2015) · Hypertension · doi:10.1161/hypertensionaha.114.04648 · Cited by 25
Renal denervation: current implications and future perspectives
Xu, J., Hering, D., Sata, Y., Walton, A., Krum, H., Esler, M., & Schlaich, M. P. (2013) · Clinical Science · doi:10.1042/cs20120581 · Cited by 24
Intrathecal capsaicin enhances one-kidney renal wrap hypertension in the rat
Burg, M., Zahm, D. S., & Knuepfer, M. M. (1994) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(94)90009-4 · Cited by 17
Campese, V. M. (2003) · Clinical and Experimental Nephrology · doi:10.1007/s10157-003-0238-y · Cited by 16
Deng, P.-Y., Yu, J., Ye, F., Li, D., Luo, D., Cai, W., Zhang, J.-W., Luo, X., Deng, H., & Li, Y. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000160218.63726.ec · Cited by 6
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Xiao, L., & Harrison, D. G. (2020) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2020.01.013 · Cited by 557
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Metadata
- 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
- Venue
- Circulation Research
- Published
- 2015-08-28
- Volume
- 117
- Issue
- 6
- Pages
- 547-557
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- 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 › Nephrology › 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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