title: Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II-Induced Hypertension.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Annet
authors.initials: A
authors.lastname: Kirabo
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Saleh
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Linjue
authors.initials: L
authors.lastname: Zhu
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Takamune
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Roxana
authors.initials: R
authors.lastname: Loperena
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Jason D
authors.initials: JD
authors.lastname: Foss
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Mernaugh
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Jackson
authors.initials: J
authors.lastname: Roberts
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: John W
authors.initials: JW
authors.lastname: Osborn
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.).
authors.forename: Hana A
authors.initials: HA
authors.lastname: Itani
authors.affiliation: From the Department of Medicine, Divisions of Clinical Pharmacology (L.X., A.K., J.W., M.A.S., L.Z., W.C., J.R., H.A.I., D.G.H.) and Nephrology and Hypertension (T.T.), Departments of Radiology and Radiological Sciences (F.W.), Molecular Physiology and Biophysics (R.L.), and Biochemistry (R.L.M.), Vanderbilt University, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia Governorate, Egypt (M.A.S.); and Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (J.D.F., J.W.O.). david.g.harrison@vanderbilt.edu.
authors.forename: David G
authors.initials: DG
authors.lastname: Harrison
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D006973:Hypertension / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000294:innervation*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D013562:Sympathectomy
chemical_list: D000804:Angiotensin II
keywords: dendritic cells; inflammation; lymphocyte; norepinephrine; sympathetic nerve block