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Cardiology Research and Practice
Volume 2012, Article ID 847172, 7 pages
http://dx.doi.org/10.1155/2012/847172
Review Article

Central Mechanisms of Abnormal Sympathoexcitation in Chronic Heart Failure

1Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
2Department of Advanced Cardiovascular Regulation and Therapeutics, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan

Received 18 May 2012; Accepted 24 June 2012

Academic Editor: Kazuko Masuo

Copyright © 2012 Takuya Kishi and Yoshitaka Hirooka. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. F. Triposkiadis, G. Karayannis, G. Giamouzis, J. Skoularigis, G. Louridas, and J. Butler, “The sympathetic nervous system in heart failure. physiology, pathophysiology, and clinical implications,” Journal of the American College of Cardiology, vol. 54, no. 19, pp. 1747–1762, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. J. S. Floras, “Sympathetic nervous system activation in human heart failure. clinical implications of an updated model,” Journal of the American College of Cardiology, vol. 54, no. 5, pp. 375–385, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. T. Kishi, “Heart failure as an autonomic nervous system dysfunction,” Journal of Cardiology, vol. 59, pp. 117–122, 2012. View at Publisher · View at Google Scholar
  4. A. M. D. Watson, S. G. Hood, and C. N. May, “Mechanisms of sympathetic activation in heart failure,” Clinical and Experimental Pharmacology and Physiology, vol. 33, no. 12, pp. 1269–1274, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. V. J. Dzau, W. S. Colucci, N. K. Hollenberg, and G. H. Williams, “Relation of the renin-angiotensin-aldosterone system to clinical state in congestive heart failure,” Circulation, vol. 63, no. 3, pp. 645–651, 1981. View at Google Scholar · View at Scopus
  6. K. Hogg and J. McMurray, “Neurohumoral pathways in heart failure with preserved systolic function,” Progress in Cardiovascular Diseases, vol. 47, no. 6, pp. 357–366, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Grassi, G. Seravalle, F. Quarti-Trevano et al., “Sympathetic and baroreflex cardiovascular control in hypertension-related left ventricular dysfunction,” Hypertension, vol. 53, no. 2, pp. 205–209, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. I. H. Zucker, H. D. Schultz, K. P. Patel, W. Wang, and L. Gao, “Regulation of central angiotensin type 1 receptors and sympathetic outflow in heart failure,” American Journal of Physiology, vol. 297, no. 5, pp. H1557–H1566, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. J. P. Fisher, C. N. Young, and P. J. Fadel, “Central sympathetic overactivity: maladies and mechanisms,” Autonomic Neuroscience, vol. 148, no. 1-2, pp. 5–15, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. I. H. Zucker, J. F. Hackley, K. G. Cornish et al., “Chronic baroreceptor activation enhances survival in dogs with pacing-induced heart failure,” Hypertension, vol. 50, no. 5, pp. 904–910, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. S. R. Houser, K. B. Margulies, A. M. Murphy et al., “Animal models of heart failure: a scientific statement from the American Heart Association,” Circulation Research, vol. 111, no. 1, pp. 131–150, 2012. View at Google Scholar
  12. P. G. Guyenet, “The sympathetic control of blood pressure,” Nature Reviews Neuroscience, vol. 7, no. 5, pp. 335–346, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. H. Wang, B. S. Huang, D. Ganten, and F. H. H. Leenen, “Prevention of sympathetic and cardiac dysfunction after myocardial infarction in transgenic rats deficient in brain angiotensinogen,” Circulation Research, vol. 94, no. 6, pp. 843–849, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. L. Hu, D. N. Zhu, Z. Yu, J. Q. Wang, Z. J. Sun, and T. Yao, “Expression of angiotensin II type 1 (AT1) receptor in the rostral ventrolateral medulla in rats,” Journal of Applied Physiology, vol. 92, no. 5, pp. 2153–2161, 2002. View at Google Scholar · View at Scopus
  15. B. S. Huang and F. H. H. Leenen, “The brain renin-angiotensin-aldosterone system: a major mechanism for sympathetic hyperactivity and left ventricular remodeling and dysfunction after myocardial infarction,” Current Heart Failure Reports, vol. 6, no. 2, pp. 81–88, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. F. H. H. Leenen, “Brain mechanisms contributing to sympathetic hyperactivity and heart failure,” Circulation Research, vol. 101, no. 3, pp. 221–223, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. A. G. Dupont and S. Brouwers, “Brain angiotensin peptides regulate sympathetic tone and blood pressure,” Journal of Hypertension, vol. 28, no. 8, pp. 1599–1610, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. V. Reja, A. K. Goodchild, J. K. Phillips, and P. M. Pilowsky, “Upregulation of angiotensin AT1 receptor and intracellular kinase gene expression in hypertensive rats,” Clinical and Experimental Pharmacology and Physiology, vol. 33, no. 8, pp. 690–695, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. A. M. Allen, I. Moeller, T. A. Jenkins et al., “Angiotensin receptors in the nervous system,” Brain Research Bulletin, vol. 47, no. 1, pp. 17–28, 1998. View at Publisher · View at Google Scholar · View at Scopus
  20. B. S. Huang, H. Zheng, J. Tan et al., “Regulation of hypothalamic renin-angiotensin system and oxidative stress by aldosterone,” Experimental Physiology, vol. 96, pp. 1028–1038, 2011. View at Publisher · View at Google Scholar
  21. L. Gao, W. Wang, Y. L. Li et al., “Sympathoexcitation by central ANG II: roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM,” American Journal of Physiology, vol. 288, no. 5, pp. H2271–H2279, 2005. View at Publisher · View at Google Scholar · View at Scopus
  22. D. Liu, L. Gao, S. K. Roy, K. G. Cornish, and I. H. Zucker, “Neuronal angiotensin II type 1 receptor upregulation in heart failure: activation of activator protein 1 and Jun N-terminal kinase,” Circulation Research, vol. 99, no. 9, pp. 1004–1011, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. Y. F. Li, W. Wang, W. G. Mayhan, and K. P. Patel, “Angiotensin-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide,” American Journal of Physiology, vol. 290, no. 4, pp. R1035–R1043, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Nozoe, Y. Hirooka, Y. Koga et al., “Inhibition of Rac1-derived reactive oxygen species in nucleus tractus solitarius decreases blood pressure and heart rate in stroke-prone spontaneously hypertensive rats,” Hypertension, vol. 50, no. 1, pp. 62–68, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. M. C. Zimmerman and I. H. Zucker, “Mitochondrial dysfunction and mitochondrial-produced reactive oxygen species new targets for neurogenic hypertension?” Hypertension, vol. 53, no. 2, pp. 112–114, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. R. A. L. Dampney, “Functional organization of central pathways regulating the cardiovascular system,” Physiological Reviews, vol. 74, no. 2, pp. 323–364, 1994. View at Google Scholar · View at Scopus
  27. T. Kishi, Y. Hirooka, Y. Kimura, K. Ito, H. Shimokawa, and A. Takeshita, “Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats,” Circulation, vol. 109, no. 19, pp. 2357–2362, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. R. Ramchandra, S. G. Hood, A. M. D. Watson et al., “Central angiotensin type 1receptor blockade decreases cardiac but not renal sympathetic nerve activity in heart failure,” Hypertension, vol. 59, pp. 634–641, 2012. View at Google Scholar
  29. L. Gao, W. Wang, D. Liu, and I. H. Zucker, “Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure,” Circulation, vol. 115, no. 24, pp. 3095–3102, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. L. Gao, W. Z. Wang, W. Wang, and I. H. Zucker, “Imbalance of angiotensin type 1 receptor and angiotensin II type 2 receptor in the rostral ventrolateral medulla potential mechanism for sympathetic overactivity in heart failure,” Hypertension, vol. 52, no. 4, pp. 708–714, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. R. B. Felder, Y. Yu, Z. H. Zhang, and S. G. Wei, “Pharmacological treatment for heart failure: a view from the brain,” Clinical Pharmacology and Therapeutics, vol. 86, no. 2, pp. 216–220, 2009. View at Publisher · View at Google Scholar · View at Scopus
  32. R. B. Felder, J. Francis, Z. H. Zhang, S. G. Wei, R. M. Weiss, and A. K. Johnson, “Heart failure and the brain: new perspectives,” American Journal of Physiology, vol. 284, no. 2, pp. R259–R276, 2003. View at Google Scholar · View at Scopus
  33. Y. Yu, Z. H. Zhang, S. G. Wei et al., “Central gene transfer of interleukin-10 reduces hypothalamic inflammation and evidence of heart failure in rats after myocardial infarction,” Circulation Research, vol. 101, no. 3, pp. 304–312, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Yu, S. G. Wei, Z. H. Zhang, E. Gomez-Sanchez, R. M. Weiss, and R. B. Felder, “Does aldosterone upregulate the brain renin-angiotensin system in rats with heart failure?” Hypertension, vol. 51, no. 3, pp. 727–733, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. S. G. Wei, Y. Yu, Z. H. Zhang, R. M. Weiss, and R. B. Felder, “Angiotensin II-triggered p44/42 mitogen-activated protein kinase mediates sympathetic excitation in heart failure rats,” Hypertension, vol. 52, no. 2, pp. 342–350, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. B. S. Huang, M. Ahmad, J. Tan, and F. H. H. Leenen, “Chronic central versus systemic blockade of AT1 receptors and cardiac dysfunction in rats post-myocardial infarction,” American Journal of Physiology, vol. 297, no. 3, pp. H968–H975, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. M. Kang, Y. Ma, C. Elks, J. P. Zheng, Z. M. Yang, and J. Francis, “Cross-talk between cytokines and renin-angiotensin in hypothalamic paraventricular nucleus in heart failure: role of nuclear factor-κB,” Cardiovascular Research, vol. 79, no. 4, pp. 671–678, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. Yu, Z. H. Zhang, S. G. Wei, J. Serrats, R. M. Weiss, and R. B. Felder, “Brain perivascular macrophages and the sympathetic response to inflammation in rats after myocardial infarction,” Hypertension, vol. 55, no. 3, pp. 652–659, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Hirooka, “Brain perivascular macrophages and central sympathetic activation after myocardial infarction: heart and brain interaction,” Hypertension, vol. 55, no. 3, pp. 610–611, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. T. Kishi, Y. Hirooka, and K. Sunagawa, “Autoimplantation of astrocytes into cardiovascular center of brainstem causes sympathoinhibition and decreases the mortality rate in hypertensive rats,” Circulation, vol. 122, Article ID A13856, 2010. View at Google Scholar
  41. T. Kishi, Y. Hirooka, and K. Sunagawa, “Autoimplantation of astrocytes into the cardiovascular center of brainstem causes sympathoinhibition and decreases the mortality rate in myocardial infarction-induced heart failure,” Circulation, vol. 124, Article ID A11489, 2011. View at Google Scholar
  42. J. P. Cardinale, S. Sriramula, N. Mariappan et al., “Angiotensin II-induced hypertension is modulated by nuclear factor-kB in the paraventricular nucleus,” Hypertension, vol. 59, pp. 113–121, 2011. View at Google Scholar
  43. P. Shi, C. Diez-Freire, J. Y. Jun et al., “Brain microglial cytokines in neurogenic hypertension,” Hypertension, vol. 56, no. 2, pp. 297–303, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. J. C. Schiltz and P. E. Sawchenko, “Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults,” Journal of Comparative Neurology, vol. 502, no. 3, pp. 455–467, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. M. L. Block, L. Zecca, and J. S. Hong, “Microglia-mediated neurotoxicity: uncovering the molecular mechanisms,” Nature Reviews Neuroscience, vol. 8, no. 1, pp. 57–69, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. Y. Yu, Z. H. Zhang, S. G. Wei et al., “Peroxisome proliferator-activated receptor-g regulates inflammation and renin-angiotensin system activity in the hypothalamic paraventricular nucleus and ameliorates peripheral manifestations of heart failure,” Hypertension, vol. 59, pp. 477–484, 2012. View at Publisher · View at Google Scholar
  47. T. Kishi, Y. Hirooka, K. Sakai, H. Shigematsu, H. Shimokawa, and A. Takeshita, “Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release,” Hypertension, vol. 38, no. 4, pp. 896–901, 2001. View at Google Scholar · View at Scopus
  48. Y. Hirooka, T. Kishi, K. Sakai, H. Shimokawa, and A. Takeshita, “Effect of overproduction of nitric oxide in the brain stem on the cardiovascular response in conscious rats,” Journal of Cardiovascular Pharmacology, vol. 41, no. 1, pp. S119–S126, 2003. View at Google Scholar · View at Scopus
  49. Y. Hirooka, H. Shigematsu, T. Kishi, Y. Kimura, Y. Ueta, and A. Takeshita, “Reduced nitric oxide synthase in the brainstem contributes to enhanced sympathetic drive in rats with heart failure,” Journal of Cardiovascular Pharmacology, vol. 42, no. 1, pp. S111–S115, 2003. View at Google Scholar · View at Scopus
  50. K. Sakai, Y. Hirooka, H. Shigematsu et al., “Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction,” American Journal of Physiology, vol. 289, no. 5, pp. H2159–H2166, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. Y. Hirooka, Y. Sagara, T. Kishi, and K. Sunagawa, “Oxidative stress and central cardiovascular regulation—pathogenesis of hypertension and therapeutic aspects,” Circulation Journal, vol. 74, no. 5, pp. 827–835, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Ito, Y. Kimura, Y. Hirooka, Y. Sagara, and K. Sunagawa, “Activation of Rho-kinase in the brainstem enhances sympathetic drive in mice with heart failure,” Autonomic Neuroscience, vol. 142, no. 1-2, pp. 77–81, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. K. Ito, Y. Hirooka, and K. Sunagawa, “Blockade of mineralocorticoid receptors improves salt-induced left-ventricular systolic dysfunction through attenuation of enhanced sympathetic drive in mice with pressure overload,” Journal of Hypertension, vol. 28, no. 7, pp. 1449–1458, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. K. Ito, Y. Hirooka, and K. Sunagawa, “Acquisition of brain na sensitivity contributes to salt-induced sympathoexcitation and cardiac dysfunction in mice with pressure overload,” Circulation Research, vol. 104, no. 8, pp. 1004–1011, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Ogawa, Y. Hirooka, T. Kishi, and K. Sunagawa, “Brain AT1 receptor activates the sympathetic nervous system through toll-like receptor 4 in mice with heart failure,” Journal of Cardiovascular Pharmacology, vol. 58, no. 5, pp. 543–549, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. S. A. Hunt, W. T. Abraham, M. H. Chin et al., “ACC/AHA, 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society,” Circulation, vol. 112, pp. e154–e235, 2005. View at Google Scholar
  57. H. F. MERIT- Investigators, “Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF),” The Lancet, vol. 353, pp. 2001–2007, 1999. View at Google Scholar
  58. H. J. Dargie, “Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial,” The Lancet, vol. 357, no. 9266, pp. 1385–1390, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Packer, M. B. Fowler, E. B. Roecker et al., “Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study,” Circulation, vol. 106, no. 17, pp. 2194–2199, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. P. A. Poole-Wilson, K. Swedberg, J. G. F. Cleland et al., “Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomised controlled trial,” The Lancet, vol. 362, no. 9377, pp. 7–13, 2003. View at Publisher · View at Google Scholar · View at Scopus
  61. R. Willenheimer, D. J. van Veldhuisen, B. Silke et al., “Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the Randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III,” Circulation, vol. 112, no. 16, pp. 2426–2435, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. J. N. Cohn, D. G. Archibald, and S. Ziesche, “Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study,” The New England Journal of Medicine, vol. 314, no. 24, pp. 1547–1552, 1986. View at Google Scholar · View at Scopus
  63. W. S. Colucci, G. H. Williams, and E. Braunwald, “Increased plasma norepinephrine levels during prazosin therapy for severe congestive heart failure,” Annals of Internal Medicine, vol. 93, no. 3, pp. 452–453, 1980. View at Google Scholar · View at Scopus
  64. ALLHAT Collaborative Research Group, “Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT),” Journal of the American Medical Association, vol. 283, no. 15, pp. 1967–1975, 2000. View at Google Scholar · View at Scopus
  65. K. Starke, M. Gothert, and H. Kilbinger, “Modulation of neurotransmitter release by presynaptic autoreceptors,” Physiological Reviews, vol. 69, no. 3, pp. 864–989, 1989. View at Google Scholar · View at Scopus
  66. T. D. Giles, M. G. Thomas, A. C. Quiroz et al., “Acute and short-term effects of clonidine in heart failure,” Angiology, vol. 38, no. 7, pp. 537–548, 1987. View at Google Scholar · View at Scopus
  67. P. Ernsberger, M. P. Meeley, and D. J. Reis, “An endogenous substance with clonidine-like properties: selective binding to imidazole sites in the ventrolateral medulla,” Brain Research, vol. 441, no. 1-2, pp. 309–318, 1988. View at Google Scholar · View at Scopus
  68. J. N. Cohn, M. A. Pfeffer, J. Rouleau et al., “Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON),” European Journal of Heart Failure, vol. 5, no. 5, pp. 659–667, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. C. Sumners and M. K. Raizada, “Angiotensin II stimulates norepinephrine uptake in hypothalamus-brain stem neuronal cultures,” American Journal of Physiology, vol. 250, no. 2, pp. C236–C244, 1986. View at Google Scholar · View at Scopus
  70. C. R. Benedict, G. S. Francis, B. Shelton et al., “Effect of long-term enalapril therapy on neurohormones in patients with left ventricular dysfunction,” American Journal of Cardiology, vol. 75, no. 16, pp. 1151–1157, 1995. View at Publisher · View at Google Scholar · View at Scopus
  71. B. Pitt, W. Remme, F. Zannad et al., “Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction,” The New England Journal of Medicine, vol. 348, no. 14, pp. 1309–1321, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. M. J. McKinley, A. L. Albiston, A. M. Allen et al., “The brain renin-angiotensin system: location and physiological roles,” International Journal of Biochemistry and Cell Biology, vol. 35, no. 6, pp. 901–918, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. T. Tsuchihashi, S. Kagiyama, K. Matsumura, I. Abe, and M. Fujishima, “Effects of chronic oral treatment with imidapril and TCV-116 on the responsiveness to angiotensin II in ventrolateral medulla of SHR,” Journal of Hypertension, vol. 17, no. 7, pp. 917–922, 1999. View at Publisher · View at Google Scholar · View at Scopus
  74. F. H. H. Leenen and B. Yuan, “Prevention of hypertension by irbesartan in Dahl S rats relates to central angiotensin II type 1 receptor blockade,” Hypertension, vol. 37, no. 3, pp. 981–984, 2001. View at Google Scholar · View at Scopus
  75. Y. Lin, K. Matsumura, S. Kagiyama, M. Fukuhara, K. Fujii, and M. Iida, “Chronic administration of olmesartan attenuates the exaggerated pressor response to glutamate in the rostral ventrolateral medulla of SHR,” Brain Research, vol. 1058, no. 1-2, pp. 161–166, 2005. View at Publisher · View at Google Scholar · View at Scopus
  76. S. Araki, Y. Hirooka, T. Kishi, K. Yasukawa, H. Utsumi, and K. Sunagawa, “Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method,” Hypertension Research, vol. 32, no. 12, pp. 1091–1096, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. T. Kishi, Y. Hirooka, and K. Sunagawa, “Sympathoinhibition caused by orally administered telmisartan through inhibition of AT(1) receptor in the rostral ventrolateral medulla,” Hypertension Research. In press.
  78. L. Gao, W. Wang, Y. L. Li et al., “Simvastatin therapy normalizes sympathetic neural control in experimental heart failure: roles of angiotensin II type 1 receptors and NAD(P)H oxidase,” Circulation, vol. 112, no. 12, pp. 1763–1770, 2005. View at Publisher · View at Google Scholar · View at Scopus
  79. R. U. Pliquett, K. G. Cornish, J. D. Peuler, and I. H. Zucker, “Simvastatin normalizes autonomic neural control in experimental heart failure,” Circulation, vol. 107, no. 19, pp. 2493–2498, 2003. View at Publisher · View at Google Scholar · View at Scopus
  80. L. Gao, W. Wang, and I. H. Zucker, “Simvastatin inhibits central sympathetic outflow in heart failure by a nitric-oxide synthase mechanism,” Journal of Pharmacology and Experimental Therapeutics, vol. 326, no. 1, pp. 278–285, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. T. Kishi, Y. Hirooka, Y. Mukai, H. Shimokawa, and A. Takeshita, “Atorvastatin causes depressor and sympatho-inhibitory effects with upregulation of nitric oxide synthases in stroke-prone spontaneously hypertensive rats,” Journal of Hypertension, vol. 21, no. 2, pp. 379–386, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Kishi, Y. Hirooka, H. Shimokawa, A. Takeshita, and K. Sunagawa, “Atorvastatin reduces oxidative stress in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats,” Clinical and Experimental Hypertension, vol. 30, no. 1, pp. 3–11, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. T. Kishi, Y. Hirooka, S. Konno et al., “Atorvastatin improves the impaired baroreflex control of stroke-prone spontaneously hypertensive rats through the anti-oxidant effect in the RVLM,” Clinical and Experimental Hypertension, vol. 31, pp. 698–704, 2009. View at Publisher · View at Google Scholar
  84. T. Kishi and Y. Hirooka, “Sympathoinhibitory effects of atorvastatin in hypertension,” Circulation Journal, vol. 74, no. 12, pp. 2552–2553, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. C. E. Negrao and H. R. Middlekauff, “Adaptations in autonomic function during exercise training in heart failure,” Heart Failure Reviews, vol. 13, no. 1, pp. 51–60, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. R. Fraga, F. G. Franco, F. Roveda et al., “Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol,” European Journal of Heart Failure, vol. 9, no. 6-7, pp. 630–636, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. C. M. O'Connor, D. J. Whellan, K. L. Lee et al., “Efficacy and safety of exercise training in patients with chronic heart failure HF-ACTION randomized controlled trial,” Journal of the American Medical Association, vol. 301, no. 14, pp. 1439–1450, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. V. Adams, C. Doring, and G. Schuler, “Impact of physical exercise on alterations in the skeletal muscle in patients with chronic heart failure,” Frontiers in Bioscience, vol. 13, no. 1, pp. 302–311, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. H. Krum, M. Schlaich, R. Whitbourn et al., “Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study,” The Lancet, vol. 373, no. 9671, pp. 1275–1281, 2009. View at Publisher · View at Google Scholar · View at Scopus
  90. G. F. DiBona and M. Esler, “Translational medicine: the antihypertensive effect of renal denervation,” American Journal of Physiology, vol. 298, no. 2, pp. R245–R253, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. Simplicity HTN-2 Investigators, “Renal sympathetic denervation in patients with treatment-resistant hypertension (The Simplicity HTN-2 Trail): a randomized controlled trial,” The Lancet, vol. 376, pp. 1903–1909, 2010. View at Google Scholar
  92. F. R. Calaresu and J. Ciriello, “Renal afferent nerves affect discharge rate of medullary and hypothalamic single units in the cat,” Journal of the Autonomic Nervous System, vol. 3, no. 2–4, pp. 311–320, 1981. View at Google Scholar · View at Scopus
  93. J. Ciriello and F. R. Calaresu, “Central projections of afferent renal fibers in the rat: an anterograde transport study of horseradish peroxidase,” Journal of the Autonomic Nervous System, vol. 8, no. 3, pp. 273–285, 1983. View at Publisher · View at Google Scholar · View at Scopus
  94. A. Stella, R. Golin, S. Genovesi, and A. Zanchetti, “Renal reflexes in the regulation of blood pressure and sodium excretion,” Canadian Journal of Physiology and Pharmacology, vol. 65, no. 8, pp. 1536–1539, 1987. View at Google Scholar · View at Scopus