Sympathetic overactivity in chronic kidney disease: Consequences and mechanisms

International Journal of Molecular Sciences

Volumn 18, Issue 8, 2017, Pages

  Kaur, Jasdeep ^a   Young, Benjamin E ^a   Fadel, Paul J ^a  

^a UNIVERSITY OF TEXAS AT ARLINGTON   (United States)

Author keywords

Angiotensin II; Asymmetric dimethylarginine; Blood pressure; Cardiovascular disease; Hypertension; Muscle sympathetic nerve activity; Nitric oxide; Oxidative stress; Sympathetic outflow

Indexed keywords

CYCLIC GMP; N(G),N(G) DIMETHYLARGININE; NITRIC OXIDE SYNTHASE; REACTIVE OXYGEN METABOLITE;

BLOOD PRESSURE; BRAIN REGION; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CAROTID SINUS PRESSORECEPTOR REFLEX; CHRONIC KIDNEY FAILURE; DIALYSIS; DISEASE ASSOCIATION; GLOMERULUS FILTRATION RATE; HUMAN; KIDNEY DENERVATION; KIDNEY TRANSPLANTATION; MORBIDITY; MUSCLE SYMPATHETIC NERVE ACTIVITY; OXIDATIVE STRESS; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SYMPATHETIC TONE; ADRENERGIC SYSTEM; ANIMAL; MORTALITY; PATHOPHYSIOLOGY; RENOVASCULAR HYPERTENSION;

ANIMALS; HUMANS; HYPERTENSION, RENAL; RENAL INSUFFICIENCY, CHRONIC; SYMPATHETIC NERVOUS SYSTEM;

EID: 85026813396     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms18081682     Document Type: Review

References (152)

1. Coresh, J.; Selvin, E.; Stevens, L.A.; Manzi, J.; Kusek, J.W.; Eggers, P.; Van, L.F.; Levey, A.S. Prevalence of chronic kidney disease in the United States. JAMA 2007, 298, 2038-2047. [CrossRef] [PubMed]
2. Saran, R.; Li, Y.; Robinson, B.; Abbott, K.C.; Agodoa, L.Y.; Ayanian, J.; Bragg-Gresham, J.; Balkrishnan, R.; Chen, J.L.; Cope, E.; et al. US Renal Data System 2015 Annual Data Report: Epidemiology of kidney disease in the United States. Am. J. Kidney Dis. 2016. [CrossRef] [PubMed]
3. Honeycutt, A.A.; Segel, J.E.; Zhuo, X.; Hoerger, T.J.; Imai, K.; Williams, D. Medical costs of CKD in the Medicare population. J. Am. Soc. Nephrol. 2013, 24, 1478-1483. [CrossRef] [PubMed]
4. Go, A.S.; Chertow, G.M.; Fan, D.; McCulloch, C.E.; Hsu, C.Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. 2004, 351, 1296-1305. [CrossRef] [PubMed]
5. Matsushita, K.; van der Velde, M.; Astor, B.C.; Woodward, M.; Levey, A.S.; de Jong, P.E.; Coresh, J.; Gansevoort, R.T. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: A collaborative meta-analysis. Lancet 2010, 375, 2073-2081. [PubMed]
6. Herzog, C.A.; Asinger, R.W.; Berger, A.K.; Charytan, D.M.; Diez, J.; Hart, R.G.; Eckardt, K.U.; Kasiske, B.L.; McCullough, P.A.; Passman, R.S.; et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2011, 80, 572-586. [CrossRef] [PubMed]
7. Green, D.; Roberts, P.R.; New, D.I.; Kalra, P.A. Sudden cardiac death in hemodialysis patients: An in-depth review. Am. J. Kidney Dis. 2011, 57, 921-929. [CrossRef] [PubMed]
8. Collins, A.J.; Foley, R.N.; Gilbertson, D.T.; Chen, S.C. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int. Suppl. 2015, 5, 2-7. [CrossRef] [PubMed]
9. Zoccali, C.; Mallamaci, F.; Parlongo, S.; Cutrupi, S.; Benedetto, F.A.; Tripepi, G.; Bonanno, G.; Rapisarda, F.; Fatuzzo, P.; Seminara, G.; et al. Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation 2002, 105, 1354-1359. [CrossRef] [PubMed]
10. Mallamaci, F.; Tripepi, G.; Maas, R.; Malatino, L.; Boger, R.; Zoccali, C. Analysis of the relationship between norepinephrine and asymmetric dimethyl arginine levels among patients with end-stage renal disease. J. Am. Soc. Nephrol. 2004, 15, 435-441. [CrossRef] [PubMed]
11. Converse, R.L., Jr.; Jacobsen, T.N.; Toto, R.D.; Jost, C.M.; Cosentino, F.; Fouad-Tarazi, F.; Victor, R.G. Sympathetic overactivity in patients with chronic renal failure. N. Engl. J. Med. 1992, 327, 1912-1918. [CrossRef] [PubMed]
12. Park, J.; Campese, V.M.; Nobakht, N.; Middlekauff, H.R. Differential distribution of muscle and skin sympathetic nerve activity in patients with end-stage renal disease. J. Appl. Physiol. 2008, 105, 1873-1876. [CrossRef] [PubMed]
13. Grassi, G.; Quarti-Trevano, F.; Seravalle, G.; Arenare, F.; Volpe, M.; Furiani, S.; Dell’Oro, R.; Mancia, G. Early sympathetic activation in the initial clinical stages of chronic renal failure. Hypertension 2011, 57, 846-851. [CrossRef] [PubMed]
14. Grassi, G.; Seravalle, G.; Ghiadoni, L.; Tripepi, G.; Bruno, R.M.; Mancia, G.; Zoccali, C. Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease. Clin. J. Am. Soc. Nephrol. 2011, 6, 2620-2627. [CrossRef] [PubMed]
15. Klein, I.H.; Ligtenberg, G.; Oey, P.L.; Koomans, H.A.; Blankestijn, P.J. Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure. J. Am. Soc. Nephrol. 2003, 14, 425-430. [CrossRef] [PubMed]
16. Ligtenberg, G.; Blankestijn, P.J.; Oey, P.L.; Klein, I.H.; Dijkhorst-Oei, L.T.; Boomsma, F.; Wieneke, G.H.; van Huffelen, A.C.; Koomans, H.A. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N. Engl. J. Med. 1999, 340, 1321-1328. [CrossRef] [PubMed]
17. Elias, A.N.; Vaziri, N.D.; Maksy, M. Plasma norepinephrine, epinephrine, and dopamine levels in end-stage renal disease. Effect of hemodialysis. Arch. Intern. Med. 1985, 145, 1013-1015. [CrossRef] [PubMed]
18. Klein, I.H.; Ligtenberg, G.; Neumann, J.; Oey, P.L.; Koomans, H.A.; Blankestijn, P.J. Sympathetic nerve activity is inappropriately increased in chronic renal disease. J. Am. Soc. Nephrol. 2003, 14, 3239-3244. [CrossRef] [PubMed]
19. Klein, I.H.; Ligtenberg, G.; Oey, P.L.; Koomans, H.A.; Blankestijn, P.J. Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension. J. Am. Soc. Nephrol. 2001, 12, 2427-2433. [PubMed]
20. Amann, K.; Rump, L.C.; Simonaviciene, A.; Oberhauser, V.; Wessels, S.; Orth, S.R.; Gross, M.L.; Koch, A.; Bielenberg, G.W.; van Kats, J.P.; et al. Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats. J. Am. Soc. Nephrol. 2000, 11, 1469-1478. [PubMed]
21. Fisher, J.P.; Young, C.N.; Fadel, P.J. Central sympathetic overactivity: Maladies and mechanisms. Auton. Neurosci. 2009, 148, 5-15. [CrossRef] [PubMed]
22. Grassi, G.; Seravalle, G.; Dell’Oro, R.; Mancia, G. Sympathetic mechanisms, organ damage, and antihypertensive treatment. Curr. Hypertens. Rep. 2011, 13, 303-308. [CrossRef] [PubMed]
23. Abboud, F.M. The sympathetic system in hypertension. State-of-the-art review. Hypertension 1982, 4, 208-225. [PubMed]
24. Smith, P.A.; Graham, L.N.; Mackintosh, A.F.; Stoker, J.B.; Mary, D.A. Relationship between central sympathetic activity and stages of human hypertension. Am. J. Hypertens. 2004, 17, 217-222. [CrossRef] [PubMed]
25. Grassi, G.; Cattaneo, B.M.; Seravalle, G.; Lanfranchi, A.; Mancia, G. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension 1998, 31, 68-72. [CrossRef] [PubMed]
26. Levey, A.S. Controlling the epidemic of cardiovascular disease in chronic renal disease: Where do we start? Am. J. Kidney Dis. 1998, 32, 5-13. [CrossRef]
27. Coresh, J.; Wei, G.L.; McQuillan, G.; Brancati, F.L.; Levey, A.S.; Jones, C.; Klag, M.J. Prevalence of high blood pressure and elevated serum creatinine level in the United States: Findings from the third National Health and Nutrition Examination Survey (1988-1994). Arch. Intern. Med. 2001, 161, 1207-1216. [CrossRef] [PubMed]
28. Feihl, F.; Liaudet, L.; Levy, B.I.; Waeber, B. Hypertension and microvascular remodelling. Cardiovasc. Res. 2008, 78, 274-285. [CrossRef] [PubMed]
29. Folkow, B. Physiological aspects of primary hypertension. Physiol. Rev. 1982, 62, 347-504. [PubMed]
30. Katholi, R.E.; Couri, D.M. Left ventricular hypertrophy: Major risk factor in patients with hypertension:Update and practical clinical applications. Int. J. Hypertens. 2011. [CrossRef] [PubMed]
31. Simpson, P. Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response. J. Clin. Investig. 1983, 72, 732-738. [CrossRef] [PubMed]
32. Raum, W.J.; Laks, M.M.; Garner, D.; Ikuhara, M.H.; Swerdloff, R.S. Norepinephrine increases β-receptors and adenylate cyclase in canine myocardium. Am. J. Physiol. 1984, 246, H31-H36. [PubMed]
33. Laks, M.M.; Morady, F.; Swan, H.J. Myocardial hypertrophy produced by chronic infusion of subhypertensive doses of norepinephrine in the dog. Chest 1973, 64, 75-78. [CrossRef] [PubMed]
34. Bevan, R.D. Effect of sympathetic denervation on smooth muscle cell proliferation in the growing rabbit ear artery. Circ. Res. 1975, 37, 14-19. [CrossRef] [PubMed]
35. Bevan, R.D. Trophic effects of peripheral adrenergic nerves on vascular structure. Hypertension 1984, 6, 19-26. [CrossRef]
36. Coutsos, M.; Sala-Mercado, J.A.; Ichinose, M.; Li, Z.; Dawe, E.J.; O’Leary, D.S. Muscle metaboreflex-induced coronary vasoconstriction limits ventricular contractility during dynamic exercise in heart failure. Am. J. Physiol. Heart Circ. Physiol. 2013, 304, 1029-1037. [CrossRef] [PubMed]
37. Volders, P.G. Novel insights into the role of the sympathetic nervous system in cardiac arrhythmogenesis. Heart Rhythm 2010, 7, 1900-1906. [CrossRef] [PubMed]
38. DiBona, G.F. Sympathetic nervous system and the kidney in hypertension. Curr. Opin. Nephrol. Hypertens. 2002, 11, 197-200. [CrossRef] [PubMed]
39. Rafiq, K.; Noma, T.; Fujisawa, Y.; Ishihara, Y.; Arai, Y.; Nabi, A.H.; Suzuki, F.; Nagai, Y.; Nakano, D.; Hitomi, H.; et al. Renal sympathetic denervation suppresses de novo podocyte injury and albuminuria in rats with aortic regurgitation. Circulation 2012, 125, 1402-1413. [CrossRef] [PubMed]
40. Jamerson, K.A.; Julius, S.; Gudbrandsson, T.; Andersson, O.; Brant, D.O. Reflex sympathetic activation induces acute insulin resistance in the human forearm. Hypertension 1993, 21, 618-623. [CrossRef] [PubMed]
41. Salzer, D.A.; Medeiros, P.J.; Craen, R.; Shoemaker, J.K. Neurogenic-nitric oxide interactions affecting brachial artery mechanics in humans: Roles of vessel distensibility vs. diameter. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008, 295, R1181-R1187. [CrossRef] [PubMed]
42. Boutouyrie, P.; Lacolley, P.; Girerd, X.; Beck, L.; Safar, M.; Laurent, S. Sympathetic activation decreases medium-sized arterial compliance in humans. Am. J. Physiol. 1994, 267, H1368-H1376. [PubMed]
43. Failla, M.; Grappiolo, A.; Emanuelli, G.; Vitale, G.; Fraschini, N.; Bigoni, M.; Grieco, N.; Denti, M.; Giannattasio, C.; Mancia, G. Sympathetic tone restrains arterial distensibility of healthy and atherosclerotic subjects. J. Hypertens. 1999, 17, 1117-1123. [CrossRef] [PubMed]
44. Thijssen, D.H.; de, G.P.; Kooijman, M.; Smits, P.; Hopman, M.T. Sympathetic nervous system contributes to the age-related impairment of flow-mediated dilation of the superficial femoral artery. Am. J. Physiol. Heart Circ. Physiol. 2006, 291, 3122-3129. [CrossRef] [PubMed]
45. Hijmering, M.L.; Stroes, E.S.; Olijhoek, J.; Hutten, B.A.; Blankestijn, P.J.; Rabelink, T.J. Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation. J. Am. Coll. Cardiol. 2002, 39, 683-688. [CrossRef]
46. Santos, A.C.; Alves, M.J.; Rondon, M.U.; Barretto, A.C.; Middlekauff, H.R.; Negrao, C.E. Sympathetic activation restrains endothelium-mediated muscle vasodilatation in heart failure patients. Am. J. Physiol. Heart Circ. Physiol. 2005, 289, 593-599. [CrossRef] [PubMed]
47. Kaplan, J.R.; Manuck, S.B. Using ethological principles to study psychosocial influences on coronary atherosclerosis in monkeys. Acta Physiol. Scand. Suppl. 1997, 640, 96-99. [PubMed]
48. Kaplan, J.R.; Manuck, S.B.; Clarkson, T.B.; Lusso, F.M.; Taub, D.M.; Miller, E.W. Social stress and atherosclerosis in normocholesterolemic monkeys. Science 1983, 220, 733-735. [CrossRef] [PubMed]
49. Strojek, K.; Grzeszczak, W.; Gorska, J.; Leschinger, M.I.; Ritz, E. Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: Novel approach to prevent progression of diabetic nephropathy? J. Am. Soc. Nephrol. 2001, 12, 602-605. [PubMed]
50. Anguiano, L.; Riera, M.; Pascual, J.; Valdivielso, J.M.; Barrios, C.; Betriu, A.; Clotet, S.; Mojal, S.; Fernandez, E.; Soler, M.J. Circulating angiotensin converting enzyme 2 activity as a biomarker of silent atherosclerosis in patients with chronic kidney disease. Atherosclerosis 2016, 253, 135-143. [CrossRef] [PubMed]
51. Medina, A.; Bell, P.R.; Briggs, J.D.; Brown, J.J.; Fine, A.; Lever, A.F.; Morton, J.J.; Paton, A.M.; Robertson, J.I.; Tree, M.; et al. Changes of blood pressure, renin, and angiotensin after bilateral nephrectomy in patients with chronic renal failure. Br. Med. J. 1972, 4, 694-696. [CrossRef] [PubMed]
52. Ibrahim, H.N.; Rosenberg, M.E.; Hostetter, T.H. Role of the renin-angiotensin-aldosterone system in the progression of renal disease: A critical review. Semin. Nephrol. 1997, 17, 431-440. [PubMed]
53. Reid, I.A. Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. Am. J. Physiol. 1992, 262, E763-E778. [PubMed]
54. Siddiqi, L.; Joles, J.A.; Grassi, G.; Blankestijn, P.J. Is kidney ischemia the central mechanism in parallel activation of the renin and sympathetic system? J. Hypertens. 2009, 27, 1341-1349. [CrossRef] [PubMed]
55. Hu, L.; Zhu, D.N.; Yu, Z.; Wang, J.Q.; Sun, Z.J.; Yao, T. Expression of angiotensin II type 1 (AT1) receptor in the rostral ventrolateral medulla in rats. J. Appl. Physiol. 2002, 92, 2153-2161. [CrossRef] [PubMed]
56. Muratani, H.; Averill, D.B.; Ferrario, C.M. Effect of angiotensin II in ventrolateral medulla of spontaneously hypertensive rats. Am. J. Physiol. 1991, 260, 977-984.
57. Hirooka, Y.; Potts, P.D.; Dampney, R.A. Role of angiotensin II receptor subtypes in mediating the sympathoexcitatory effects of exogenous and endogenous angiotensin peptides in the rostral ventrolateral medulla of the rabbit. Brain Res. 1997, 772, 107-114. [CrossRef]
58. Allen, A.M. Blockade of angiotensin AT1-receptors in the rostral ventrolateral medulla of spontaneously hypertensive rats reduces blood pressure and sympathetic nerve discharge. J. Renin Angiotensin Aldosterone Syst. 2001, 2, 120-124. [CrossRef] [PubMed]
59. Allen, A.M.; Moeller, I.; Jenkins, T.A.; Zhuo, J.; Aldred, G.P.; Chai, S.Y.; Mendelsohn, F.A. Angiotensin receptors in the nervous system. Brain Res. Bull. 1998, 47, 17-28. [CrossRef]
60. Davisson, R.L. Physiological genomic analysis of the brain renin-angiotensin system. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003, 285, 498-511. [CrossRef] [PubMed]
61. Campese, V.M.; Kogosov, E. Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension 1995, 25, 878-882. [CrossRef] [PubMed]
62. Ye, S.; Zhong, H.; Yanamadala, V.; Campese, V.M. Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity. Am. J. Hypertens. 2002, 15, 717-724. [CrossRef]
63. Ye, S.; Ozgur, B.; Campese, V.M. Renal afferent impulses, the posterior hypothalamus, and hypertension in rats with chronic renal failure. Kidney Int. 1997, 51, 722-727. [CrossRef] [PubMed]
64. Ye, S.; Zhong, H.; Yanamadala, S.; Campese, V.M. Oxidative stress mediates the stimulation of sympathetic nerve activity in the phenol renal injury model of hypertension. Hypertension 2006, 48, 309-315. [CrossRef] [PubMed]
65. Katholi, R.E.; Whitlow, P.L.; Hageman, G.R.; Woods, W.T. Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves in the dog. J. Hypertens. 1984, 2, 349-359. [CrossRef] [PubMed]
66. Recordati, G.; Moss, N.G.; Genovesi, S.; Rogenes, P. Renal chemoreceptors. J. Auton. Nerv. Syst. 1981, 3, 237-251. [CrossRef]
67. Vallon, V.; Muhlbauer, B.; Osswald, H. Adenosine and kidney function. Physiol. Rev. 2006, 86, 901-940. [CrossRef] [PubMed]
68. Hausberg, M.; Kosch, M.; Harmelink, P.; Barenbrock, M.; Hohage, H.; Kisters, K.; Dietl, K.H.; Rahn, K.H. Sympathetic nerve activity in end-stage renal disease. Circulation 2002, 106, 1974-1979. [CrossRef] [PubMed]
69. Desir, G.V.; Peixoto, A.J. Renalase in hypertension and kidney disease. Nephrol. Dial. Transplant. 2014, 29, 22-28. [CrossRef] [PubMed]
70. Xu, J.; Li, G.; Wang, P.; Velazquez, H.; Yao, X.; Li, Y.; Wu, Y.; Peixoto, A.; Crowley, S.; Desir, G.V. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J. Clin. Investig. 2005, 115, 1275-1280. [CrossRef] [PubMed]
71. Desir, G.V. Renalase deficiency in chronic kidney disease, and its contribution to hypertension and cardiovascular disease. Curr. Opin. Nephrol. Hypertens. 2008, 17, 181-185. [CrossRef] [PubMed]
72. Li, G.; Xu, J.; Wang, P.; Velazquez, H.; Li, Y.; Wu, Y.; Desir, G.V. Catecholamines regulate the activity, secretion, and synthesis of renalase. Circulation 2008, 117, 1277-1282. [CrossRef] [PubMed]
73. Mungrue, I.N.; Bredt, D.S.; Stewart, D.J.; Husain, M. From molecules to mammals: What’s NOS got to do with it? Acta Physiol. Scand. 2003, 179, 123-135. [CrossRef] [PubMed]
74. Sakuma, I.; Togashi, H.; Yoshioka, M.; Saito, H.; Yanagida, M.; Tamura, M.; Kobayashi, T.; Yasuda, H.; Gross, S.S.; Levi, R. NG-methyl-L-arginine, an inhibitor of L-arginine-derived nitric oxide synthesis, stimulates renal sympathetic nerve activity in vivo. A role for nitric oxide in the central regulation of sympathetic tone? Circ. Res. 1992, 70, 607-611. [CrossRef] [PubMed]
75. Sander, M.; Hansen, J.; Victor, R.G. The sympathetic nervous system is involved in the maintenance but not initiation of the hypertension induced by N(omega)-nitro-L-arginine methyl ester. Hypertension 1997, 30, 64-70. [CrossRef] [PubMed]
76. Sander, M.; Chavoshan, B.; Victor, R.G. A large blood pressure-raising effect of nitric oxide synthase inhibition in humans. Hypertension 1999, 33, 937-942. [CrossRef] [PubMed]
77. Cannon, R.O., III. Role of nitric oxide in cardiovascular disease: Focus on the endothelium. Clin. Chem. 1998, 44, 1809-1819. [PubMed]
78. Cooke, J.P.; Dzau, V.J. Nitric oxide synthase: Role in the genesis of vascular disease. Annu. Rev. Med. 1997, 48, 489-509. [CrossRef] [PubMed]
79. Shapoval, L.N.; Sagach, V.F.; Pobegailo, L.S. Nitric oxide influences ventrolateral medullary mechanisms of vasomotor control in the cat. Neurosci. Lett. 1991, 132, 47-50. [CrossRef]
80. Harada, S.; Tokunaga, S.; Momohara, M.; Masaki, H.; Tagawa, T.; Imaizumi, T.; Takeshita, A. Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits. Circ. Res. 1993, 72, 511-516. [CrossRef] [PubMed]
81. Tagawa, T.; Imaizumi, T.; Harada, S.; Endo, T.; Shiramoto, M.; Hirooka, Y.; Takeshita, A. Nitric oxide influences neuronal activity in the nucleus tractus solitarius of rat brainstem slices. Circ. Res. 1994, 75, 70-76. [CrossRef] [PubMed]
82. Togashi, H.; Sakuma, I.; Yoshioka, M.; Kobayashi, T.; Yasuda, H.; Kitabatake, A.; Saito, H.; Gross, S.S.; Levi, R. A central nervous system action of nitric oxide in blood pressure regulation. J. Pharmacol. Exp. Ther. 1992, 262, 343-347. [PubMed]
83. Kishi, T.; Hirooka, Y.; Sakai, K.; Shigematsu, H.; Shimokawa, H.; Takeshita, A. Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release. Hypertension 2001, 38, 896-901. [PubMed]
84. Kishi, T.; Hirooka, Y.; Ito, K.; Sakai, K.; Shimokawa, H.; Takeshita, A. Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive rats. Hypertension 2002, 39, 264-268. [CrossRef] [PubMed]
85. Kumagai, H.; Averill, D.B.; Khosla, M.C.; Ferrario, C.M. Role of nitric oxide and angiotensin II in the regulation of sympathetic nerve activity in spontaneously hypertensive rats. Hypertension 1993, 21, 476-484. [CrossRef] [PubMed]
86. Hansen, J.; Jacobsen, T.N.; Victor, R.G. Is nitric oxide involved in the tonic inhibition of central sympathetic outflow in humans? Hypertension 1994, 24, 439-444. [CrossRef] [PubMed]
87. Augustyniak, R.A.; Victor, R.G.; Morgan, D.A.; Zhang, W. L-NAME and ADMA-induced sympathetic neural activation in conscious rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006, 290, R726-R732. [CrossRef] [PubMed]
88. Young, C.N.; Fisher, J.P.; Gallagher, K.M.; Whaley-Connell, A.; Chaudhary, K.; Victor, R.G.; Thomas, G.D.; Fadel, P.J. Inhibition of nitric oxide synthase evokes central sympatho-excitation in healthy humans. J. Physiol. 2009, 587, 4977-4986. [CrossRef] [PubMed]
89. Xiao, S.; Wagner, L.; Schmidt, R.J.; Baylis, C. Circulating endothelial nitric oxide synthase inhibitory factor in some patients with chronic renal disease. Kidney Int. 2001, 59, 1466-1472. [CrossRef] [PubMed]
90. Kielstein, J.T.; Boger, R.H.; Bode-Boger, S.M.; Frolich, J.C.; Haller, H.; Ritz, E.; Fliser, D. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J. Am. Soc. Nephrol. 2002, 13, 170-176. [PubMed]
91. Ravani, P.; Tripepi, G.; Malberti, F.; Testa, S.; Mallamaci, F.; Zoccali, C. Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: A competing risks modeling approach. J. Am. Soc. Nephrol. 2005, 16, 2449-2455. [CrossRef] [PubMed]
92. Ueda, S.; Yamagishi, S.; Kaida, Y.; Okuda, S. Asymmetric dimethylarginine may be a missing link between cardiovascular disease and chronic kidney disease. Nephrology 2007, 12, 582-590. [CrossRef] [PubMed]
93. Zoccali, C. Asymmetric dimethylarginine (ADMA): A cardiovascular and renal risk factor on the move. J. Hypertens. 2006, 24, 611-619. [CrossRef] [PubMed]
94. Zoccali, C.; Bode-Boger, S.; Mallamaci, F.; Benedetto, F.; Tripepi, G.; Malatino, L.; Cataliotti, A.; Bellanuova, I.; Fermo, I.; Frolich, J.; et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: A prospective study. Lancet 2001, 358, 2113-2117. [CrossRef]
95. Fliser, D.; Kronenberg, F.; Kielstein, J.T.; Morath, C.; Bode-Boger, S.M.; Haller, H.; Ritz, E. Asymmetric dimethylarginine and progression of chronic kidney disease: The mild to moderate kidney disease study. J. Am. Soc. Nephrol. 2005, 16, 2456-2461. [CrossRef] [PubMed]
96. Boger, R.H.; Bode-Boger, S.M.; Szuba, A.; Tsao, P.S.; Chan, J.R.; Tangphao, O.; Blaschke, T.F.; Cooke, J.P. Asymmetric dimethylarginine (ADMA): A novel risk factor for endothelial dysfunction: Its role in hypercholesterolemia. Circulation 1998, 98, 1842-1847. [CrossRef] [PubMed]
97. Young, J.M.; Terrin, N.; Wang, X.; Greene, T.; Beck, G.J.; Kusek, J.W.; Collins, A.J.; Sarnak, M.J.; Menon, V. Asymmetric dimethylarginine and mortality in stages 3 to 4 chronic kidney disease. Clin. J. Am. Soc. Nephrol. 2009, 4, 1115-1120. [CrossRef] [PubMed]
98. Watson, C.P.; Pazarentzos, E.; Fidanboylu, M.; Padilla, B.; Brown, R.; Thomas, S.A. The transporter and permeability interactions of asymmetric dimethylarginine (ADMA) and L-arginine with the human blood-brain barrier in vitro. Brain Res. 2016, 1648, 232-242. [CrossRef] [PubMed]
99. Vallance, P.; Leiper, J. Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler. Thromb. Vasc. Biol. 2004, 24, 1023-1030. [CrossRef] [PubMed]
100. Tran, C.T.; Leiper, J.M.; Vallance, P. The DDAH/ADMA/NOS pathway. Atheroscler. Suppl. 2003, 4, 33-40. [CrossRef]
101. Achan, V.; Broadhead, M.; Malaki, M.; Whitley, G.; Leiper, J.; MacAllister, R.; Vallance, P. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler. Thromb. Vasc. Biol. 2003, 23, 1455-1459. [CrossRef] [PubMed]
102. Dounousi, E.; Papavasiliou, E.; Makedou, A.; Ioannou, K.; Katopodis, K.P.; Tselepis, A.; Siamopoulos, K.C.; Tsakiris, D. Oxidative stress is progressively enhanced with advancing stages of CKD. Am. J. Kidney Dis. 2006, 48, 752-760. [CrossRef] [PubMed]
103. Oberg, B.P.; McMenamin, E.; Lucas, F.L.; McMonagle, E.; Morrow, J.; Ikizler, T.A.; Himmelfarb, J. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004, 65, 1009-1016. [CrossRef] [PubMed]
104. Himmelfarb, J.; Stenvinkel, P.; Ikizler, T.A.; Hakim, R.M. The elephant in uremia: Oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int. 2002, 62, 1524-1538. [CrossRef] [PubMed]
105. Martinez Cantarin, M.P.; Whitaker-Menezes, D.; Lin, Z.; Falkner, B. Uremia induces adipose tissue inflammation and muscle mitochondrial dysfunction. Nephrol. Dial. Transplant. 2017, 32, 943-951. [CrossRef] [PubMed]
106. Takahashi, N.; Morimoto, S.; Okigaki, M.; Seo, M.; Someya, K.; Morita, T.; Matsubara, H.; Sugiura, T.; Iwasaka, T. Decreased plasma level of vitamin C in chronic kidney disease: Comparison between diabetic and non-diabetic patients. Nephrol. Dial. Transplant. 2011, 26, 1252-1257. [CrossRef] [PubMed]
107. Hirooka, Y.; Kishi, T.; Sakai, K.; Takeshita, A.; Sunagawa, K. Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011, 300, R818-R826. [CrossRef] [PubMed]
108. Oliveira-Sales, E.B.; Nishi, E.E.; Carillo, B.A.; Boim, M.A.; Dolnikoff, M.S.; Bergamaschi, C.T.; Campos, R.R. Oxidative stress in the sympathetic premotor neurons contributes to sympathetic activation in renovascular hypertension. Am. J. Hypertens. 2009, 22, 484-492. [CrossRef] [PubMed]
109. Nishihara, M.; Hirooka, Y.; Matsukawa, R.; Kishi, T.; Sunagawa, K. Oxidative stress in the rostral ventrolateral medulla modulates excitatory and inhibitory inputs in spontaneously hypertensive rats. J. Hypertens. 2012, 30, 97-106. [CrossRef] [PubMed]
110. Kishi, T.; Hirooka, Y.; Kimura, Y.; Ito, K.; Shimokawa, H.; Takeshita, A. Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats. Circulation 2004, 109, 2357-2362. [CrossRef] [PubMed]
111. Campese, V.M.; Ye, S.; Zhong, H.; Yanamadala, V.; Ye, Z.; Chiu, J. Reactive oxygen species stimulate central and peripheral sympathetic nervous system activity. Am. J. Physiol. Heart Circ. Physiol. 2004, 287, 695-703. [CrossRef] [PubMed]
112. Griendling, K.K.; Minieri, C.A.; Ollerenshaw, J.D.; Alexander, R.W. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ. Res. 1994, 74, 1141-1148. [CrossRef] [PubMed]
113. Campese, V.M.; Shaohua, Y.; Huiquin, Z. Oxidative stress mediates angiotensin II-dependent stimulation of sympathetic nerve activity. Hypertension 2005, 46, 533-539. [CrossRef] [PubMed]
114. Chan, S.H.; Hsu, K.S.; Huang, C.C.; Wang, L.L.; Ou, C.C.; Chan, J.Y. NADPH oxidase-derived superoxide anion mediates angiotensin II-induced pressor effect via activation of p38 mitogen-activated protein kinase in the rostral ventrolateral medulla. Circ. Res. 2005, 97, 772-780. [CrossRef] [PubMed]
115. Patel, K.P.; Mayhan, W.G.; Bidasee, K.R.; Zheng, H. Enhanced angiotensin II-mediated central sympathoexcitation in streptozotocin-induced diabetes: Role of superoxide anion. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011, 300, R311-R320. [CrossRef] [PubMed]
116. Zimmerman, M.C.; Lazartigues, E.; Lang, J.A.; Sinnayah, P.; Ahmad, I.M.; Spitz, D.R.; Davisson, R.L. Superoxide mediates the actions of angiotensin II in the central nervous system. Circ. Res. 2002, 91, 1038-1045. [CrossRef] [PubMed]
117. Shi, Z.; Chen, A.D.; Xu, Y.; Chen, Q.; Gao, X.Y.; Wang, W.; Zhu, G.Q. Long-term administration of tempol attenuates postinfarct ventricular dysfunction and sympathetic activity in rats. Pflug. Arch. 2009, 458, 247-257. [CrossRef] [PubMed]
118. Wei, S.G.; Zhang, Z.H.; Yu, Y.; Felder, R.B. Systemically administered tempol reduces neuronal activity in paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in rats. J. Hypertens. 2009, 27, 543-550. [CrossRef] [PubMed]
119. Ito, A.; Tsao, P.S.; Adimoolam, S.; Kimoto, M.; Ogawa, T.; Cooke, J.P. Novel mechanism for endothelial dysfunction: Dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 1999, 99, 3092-3095. [CrossRef] [PubMed]
120. Cohn, J.N.; Pfeffer, M.A.; Rouleau, J.; Sharpe, N.; Swedberg, K.; Straub, M.; Wiltse, C.; Wright, T.J. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur. J. Heart Fail. 2003, 5, 659-667. [CrossRef]
121. Planitz, V. Crossover comparison of moxonidine and clonidine in mild to moderate hypertension. Eur. J. Clin. Pharmacol. 1984, 27, 147-152. [CrossRef] [PubMed]
122. Swedberg, K.; Bristow, M.R.; Cohn, J.N.; Dargie, H.; Straub, M.; Wiltse, C.; Wright, T.J. Effects of sustained-release moxonidine, an imidazoline agonist, on plasma norepinephrine in patients with chronic heart failure. Circulation 2002, 105, 1797-1803. [CrossRef] [PubMed]
123. Gao, L.; Wang, W.; Li, Y.L.; Schultz, H.D.; Liu, D.; Cornish, K.G.; Zucker, I.H. Simvastatin therapy normalizes sympathetic neural control in experimental heart failure: Roles of angiotensin II type 1 receptors and NAD(P)H oxidase. Circulation 2005, 112, 1763-1770. [CrossRef] [PubMed]
124. Gao, L.; Wang, W.; Zucker, I.H. Simvastatin inhibits central sympathetic outflow in heart failure by a nitric-oxide synthase mechanism. J. Pharmacol. Exp. Ther. 2008, 326, 278-285. [CrossRef] [PubMed]
125. Deo, S.H.; Fisher, J.P.; Vianna, L.C.; Kim, A.; Chockalingam, A.; Zimmerman, M.C.; Zucker, I.H.; Fadel, P.J. Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in patients with heart failure. Am. J. Physiol. Heart Circ. Physiol. 2012, 303, 377-385. [CrossRef] [PubMed]
126. Lewandowski, J.; Symonides, B.; Gaciong, Z.; Sinski, M. The effect of statins on sympathetic activity:A meta-analysis. Clin. Auton. Res. 2015, 25, 125-131. [CrossRef] [PubMed]
127. Siddiqi, L.; Joles, J.A.; Oey, P.L.; Blankestijn, P.J. Atorvastatin reduces sympathetic activity in patients with chronic kidney disease. J. Hypertens. 2011, 29, 2176-2180. [CrossRef] [PubMed]
128. Chung, C.M.; Lin, M.S.; Hsu, J.T.; Hsiao, J.F.; Chang, S.T.; Pan, K.L.; Lin, C.L.; Lin, Y.S. Effects of statin therapy on cerebrovascular and renal outcomes in patients with predialysis advanced chronic kidney disease and dyslipidemia. J. Clin. Lipidol. 2017, 11, 422-431. [CrossRef] [PubMed]
129. Major, R.W.; Cheung, C.K.; Gray, L.J.; Brunskill, N.J. Statins and Cardiovascular Primary Prevention in CKD:A Meta-Analysis. Clin. J. Am. Soc. Nephrol. 2015, 10, 732-739. [CrossRef] [PubMed]
130. Messow, C.M.; Isles, C. Meta-analysis of statins in chronic kidney disease: Who benefits? QJM 2017. [CrossRef] [PubMed]
131. Boaz, M.; Smetana, S.; Weinstein, T.; Matas, Z.; Gafter, U.; Iaina, A.; Knecht, A.; Weissgarten, Y.; Brunner, D.; Fainaru, M.; et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): Randomised placebo-controlled trial. Lancet 2000, 356, 1213-1218. [CrossRef]
132. Bruno, R.M.; Daghini, E.; Ghiadoni, L.; Sudano, I.; Rugani, I.; Varanini, M.; Passino, C.; Emdin, M.; Taddei, S. Effect of acute administration of vitamin C on muscle sympathetic activity, cardiac sympathovagal balance, and baroreflex sensitivity in hypertensive patients. Am. J. Clin. Nutr. 2012, 96, 302-308. [CrossRef] [PubMed]
133. Gomes, M.E.; El, M.S.; Lenders, J.W.; Bellersen, L.; Verheugt, F.W.; Smits, P.; Tack, C.J. High dose ascorbic acid does not reverse central sympathetic overactivity in chronic heart failure. J. Clin. Pharm. Ther. 2011, 36, 546-552. [CrossRef] [PubMed]
134. Singer, R.F. Vitamin C supplementation in kidney failure: Effect on uraemic symptoms. Nephrol. Dial. Transplant. 2011, 26, 614-620. [CrossRef] [PubMed]
135. Tahara, N.; Yamagishi, S.; Mizoguchi, M.; Tahara, A.; Imaizumi, T. Pioglitazone decreases asymmetric dimethylarginine levels in patients with impaired glucose tolerance or type 2 diabetes. Rejuvenation Res. 2013, 16, 344-351. [CrossRef] [PubMed]
136. Wakino, S.; Hayashi, K.; Tatematsu, S.; Hasegawa, K.; Takamatsu, I.; Kanda, T.; Homma, K.; Yoshioka, K.; Sugano, N.; Saruta, T. Pioglitazone lowers systemic asymmetric dimethylarginine by inducing dimethylarginine dimethylaminohydrolase in rats. Hypertens Res. 2005, 28, 255-262. [CrossRef] [PubMed]
137. Esler, M.D.; Krum, H.; Sobotka, P.A.; Schlaich, M.P.; Schmieder, R.E.; Bohm, M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The symplicity HTN-2 trial): A randomised controlled trial. Lancet 2010, 376, 1903-1909. [PubMed]
138. Krum, H.; Schlaich, M.; Whitbourn, R.; Sobotka, P.A.; Sadowski, J.; Bartus, K.; Kapelak, B.; Walton, A.; Sievert, H.; Thambar, S.; et al. Catheter-based renal sympathetic denervation for resistant hypertension:A multicentre safety and proof-of-principle cohort study. Lancet 2009, 373, 1275-1281. [CrossRef]
139. Jacob, F.; Ariza, P.; Osborn, J.W. Renal denervation chronically lowers arterial pressure independent of dietary sodium intake in normal rats. Am. J. Physiol. Heart Circ. Physiol. 2003, 284, H2302-H2310. [CrossRef] [PubMed]
140. Ojeda, N.B.; Johnson, W.R.; Dwyer, T.M.; Alexander, B.T. Early renal denervation prevents development of hypertension in growth-restricted offspring. Clin. Exp. Pharmacol. Physiol. 2007, 34, 1212-1216. [CrossRef] [PubMed]
141. Katholi, R.E.; Rocha-Singh, K.J. The role of renal sympathetic nerves in hypertension: Has percutaneous renal denervation refocused attention on their clinical significance? Prog. Cardiovasc. Dis. 2009, 52, 243-248. [CrossRef] [PubMed]
142. Hendel, M.D.; Collister, J.P. Renal denervation attenuates long-term hypertensive effects of Angiotensin II in the rat. Clin. Exp. Pharmacol. Physiol. 2006, 33, 1225-1230. [CrossRef] [PubMed]
143. Lohmeier, T.E.; Hildebrandt, D.A.; Dwyer, T.M.; Barrett, A.M.; Irwin, E.D.; Rossing, M.A.; Kieval, R.S. Renal denervation does not abolish sustained baroreflex-mediated reductions in arterial pressure. Hypertension 2007, 49, 373-379. [CrossRef] [PubMed]
144. 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. A controlled trial of renal denervation for resistant hypertension. N. Engl. J. Med. 2014, 370, 1393-1401. [CrossRef] [PubMed]
145. Hering, D.; Mahfoud, F.; Walton, A.S.; Krum, H.; Lambert, G.W.; Lambert, E.A.; Sobotka, P.A.; Bohm, M.; Cremers, B.; Esler, M.D.; et al. Renal denervation in moderate to severe CKD. J. Am. Soc. Nephrol. 2012, 23, 1250-1257. [CrossRef] [PubMed]
146. Papademetriou, V.; Doumas, M.; Anyfanti, P.; Faselis, C.; Kokkinos, P.; Tsioufis, C. Renal nerve ablation for hypertensive patients with chronic kidney disease. Curr. Vasc. Pharmacol. 2014, 12, 47-54. [PubMed]
147. Gattone, V.H.; Siqueira, T.M., Jr.; Powell, C.R.; Trambaugh, C.M.; Lingeman, J.E.; Shalhav, A.L. Contribution of renal innervation to hypertension in rat autosomal dominant polycystic kidney disease. Exp. Biol. Med. 2008, 233, 952-957. [CrossRef] [PubMed]
148. Kiuchi, M.G.; Maia, G.L.; de Queiroz Carreira, M.A.; Kiuchi, T.; Chen, S.; Andrea, B.R.; Graciano, M.L.; Lugon, J.R. Effects of renal denervation with a standard irrigated cardiac ablation catheter on blood pressure and renal function in patients with chronic kidney disease and resistant hypertension. Eur. Heart J. 2013, 34, 2114-2121. [CrossRef] [PubMed]
149. Schlaich, M.P.; Bart, B.; Hering, D.; Walton, A.; Marusic, P.; Mahfoud, F.; Bohm, M.; Lambert, E.A.; Krum, H.; Sobotka, P.A.; et al. Feasibility of catheter-based renal nerve ablation and effects on sympathetic nerve activity and blood pressure in patients with end-stage renal disease. Int. J. Cardiol. 2013, 168, 2214-2220. [CrossRef] [PubMed]
150. Lohmeier, T.E.; Iliescu, R.; Dwyer, T.M.; Irwin, E.D.; Cates, A.W.; Rossing, M.A. Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex. Am. J. Physiol. Heart Circ. Physiol. 2010, 299, 402-409. [CrossRef] [PubMed]
151. Heusser, K.; Tank, J.; Engeli, S.; Diedrich, A.; Menne, J.; Eckert, S.; Peters, T.; Sweep, F.C.; Haller, H.; Pichlmaier, A.M.; et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension 2010, 55, 619-626. [CrossRef] [PubMed]
152. Bisognano, J.D.; Bakris, G.; Nadim, M.K.; Sanchez, L.; Kroon, A.A.; Schafer, J.; de Leeuw, P.W.; Sica, D.A. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: Results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J. Am. Coll. Cardiol. 2011, 58, 765-773. [CrossRef] [PubMed]