Oxidative Stress and Central Regulation of Blood Pressure

Chapter
First Online:
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

It is well established that oxidative stress is involved in the pathogenesis of hypertension. With regard to oxidative stress, however, much attention has been focused on vascular damage in the process of hypertension. In consecutive studies, we have been investigating the role of brain oxidative stress in the central nervous system control of blood pressure. Indeed, we found that oxidative stress is increased in the brain stem, thereby activating the sympathetic nervous system, leading to hypertension. In this chapter, we describe our series of consecutive studies regarding this issue and supporting reports from other laboratories. Because of the importance of sympathetic activation for hypertensive vascular damage, our concepts not only of the pathogenesis but also the therapeutic aspects of hypertension are worthy of attention.

Keywords

Oxidative stress Blood pressure Hypertension Heart rate Sympathetic nervous system Brain Rostral ventrolateral medulla Reactive oxygen species Metabolic syndrome Heart failure 
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Notes

Acknowledgments

The series of studies was supported by Grants-in Aid for Scientific Research from the Japan Society for the Promotion of Science (B193290231, B24390198). The Department of Advanced Cardiovascular Regulation and Therapeutics, Kyushu University is supported by Actelion Pharmaceuticals Ltd (Y.H.).

References

  1. 1.
    Araki S, Hirooka Y, Kishi T, Yasukawa K, Utsumi H, Sunagawa K. Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method. Hypertens Res. 2009;32:1091–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Chan SHH, Chan JYH. Brain stem oxidative stress and its associated signaling in the regulation of sympathetic vasomotor tone. J Appl Physiol. 2012;113:1921–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Chan SHH, Chan JYH. Brain stem NOS and ROS in neural mechanisms of hypertension. Antioxid Redox Signal. 2014;20:146–63.CrossRefPubMedGoogle Scholar
  4. 4.
    Francis J, Davisson RL. Emerging concepts in hypertension. Antioxid Redox Signal. 2014;20:69–73.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Fujita M, Fujita T. The role of CNS in salt-sensitive hypertension. Curr Hypertens Rep. 2013;15:390–4.CrossRefPubMedGoogle Scholar
  6. 6.
    Gabor A, Leenen FHH. Central neuromodulatory pathways regulating sympathetic activity in hypertension. J Appl Physiol. 2012;113:1294–303.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hirooka Y. Localized gene transfer and its application for the study of central cardiovascular control. Auton Neurosci. 2006;126/127:120–9.CrossRefGoogle Scholar
  8. 8.
    Hirooka Y. Role of reactive oxygen species in brainstem in neural mechanisms of hypertension. Auton Neurosci. 2008;142:20–4.CrossRefPubMedGoogle Scholar
  9. 9.
    Hirooka Y. Oxidative stress in the cardiovascular center has a pivotal role in the sympathetic activation in hypertension. Hypertens Res. 2011;34:407–12.CrossRefPubMedGoogle Scholar
  10. 10.
    Hirooka Y, Kimura Y, Nozoe M, Sagara Y, Ito K, Sunagawa K. Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats. Hypertens Res. 2006;29:49–56.CrossRefPubMedGoogle Scholar
  11. 11.
    Hirooka Y, Sagara Y, Kishi T, Sunagawa K. Oxidative stress and central cardiovascular regulation-pathogenesis of hypertension and therapeutic aspects. Circ J. 2010;74:827–35.CrossRefPubMedGoogle Scholar
  12. 12.
    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:R818–26.CrossRefPubMedGoogle Scholar
  13. 13.
    Hirooka Y, Kishi T, Ito K, Sunagawa K. Potential clinical application of recently discovered brain mechanisms involved in hypertension. Hypertension. 2013;62:995–1002.CrossRefPubMedGoogle Scholar
  14. 14.
    Honda N, Hirooka Y, Ito K, Matsukawa R, Shinohara K, Kishi T, et al. Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure. J Hypertens. 2013;31:2300–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Isegawa K, Hirooka Y, Katsuki M, Kishi T, Sunagawa K. Angiotensin type 1 receptor expression in astrocytes is upregulated leading to increased mortality in mice with myocardial infarction-induced heart failure. Am J Physiol Heart Circ Physiol. 2014;307:H1448–55.CrossRefPubMedGoogle Scholar
  16. 16.
    Kimura Y, Hirooka Y, Sagara Y, Ito K, Kishi T, Shimokawa H, et al. Ocerexpression of inducible nitric oxide synthase in rostral ventrolateral medulla causes hypertension and sympathoexcitation via an increase in oxidative stress. Circ Res. 2005;96:252–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Kimura Y, Hirooka Y, Kishi T, Ito K, Sagara Y, Sunagawa K. Role of inducible synthase in rostral ventrolateral medulla in blood pressure regulation in spontaneously hypertensive rats. Clin Exp Hypertens. 2009;31:281–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Kishi T, Hirooka Y, Kimura Y, Ito K, Shimokawa H, Takeshita A. Increased reactive oxygen species in rostral ventrolaterla medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats. Circulation. 2004;109:2357–62.CrossRefPubMedGoogle Scholar
  19. 19.
    Kishi T, Hirooka Y, Shimokawa H, Takeshita A, Sunagawa K. Atorvastatin reduces oxidative stress in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats. Clin Exp Hypertens. 2008;30:3–11.CrossRefPubMedGoogle Scholar
  20. 20.
    Kishi T, Hirooka Y, Konno S, Sunagawa K. Atorvastatin improves the impaired baroreflex sensitivity via anti-oxidant effect in the rostral ventrolateral medulla of SHRSP. Clin Exp Hypertens. 2009;31:698–704.CrossRefPubMedGoogle Scholar
  21. 21.
    Kishi T, Hirooka Y, Konno S, Ogawa K, Sunagawa K. Angiotensin II type 1 receptor-activated caspase-3 through ras/mitogen-activated protein kinase/extracellular signal-regulated kinase in the rostral ventrolateral medulla is involved in sympathoexcitation in stroke-prone spontaneously hypertensive rats. Hypertension. 2010;55:291–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Kishi T, Hirooka Y, Ogawa K, Konno S, Sunagawa K. Calorie restriction inhibits sympathetic nerve activity via anti-oxidant effect in the rostral ventrolateral medulla of obesity-induced hypertensive rats. Clin Exp Hypertens. 2011;33:240–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Kishi T, Hirooka Y, Sunagawa K. Sympathoinhibition caused by orally administered telmisartan through inhibition of the AT1 receptor in the rostral ventrolateral medulla of hypertensive rats. Hypertens Res. 2012;35:940–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Kishi T, Hirooka Y, Sunagwa K. Telmisartan reduces mortality and left ventricular hypertrophy with sympathoinhibition in rats with hypertension and heart failure. Am J Hypertens. 2014;27:260–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Koga Y, Hirooka Y, Araki S, Nozoe M, Kishi T, Sunagawa K. High salt intake enhances blood pressure increase during development of hypertension via oxidative stress in rostral ventrolateral medulla of spontaneously hypertensive rats. Hypertens Res. 2008;31:2075–83.CrossRefPubMedGoogle Scholar
  26. 26.
    Konno S, Hirooka Y, Araki S, Koga Y, Kishi T, Sunagawa K. Azelnidipine decreases sympathetic nerve activity via antioxidant effect in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats. J Cardiovasc Pharamacol. 2008;52:555–60.CrossRefGoogle Scholar
  27. 27.
    Konno S, Hirooka Y, Kishi T, Sunagawa K. Sympathoinhibitory effects of telmisartan through the reduction of oxidative stress in the rostral ventrolateral medulla of obesity-induced hypertensive rats. J Hypertens. 2012;30:1992–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Montezano AC, Touyz RM. Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research. Antioxid Redox Signal. 2014;20:164–82.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Nagayama T, Hirooka Y, Kishi T, Mukai Y, Inoue S, Takase S, et al. Blockade of brain angiotensin II type 1 receptor inhibits the development of atrial fibrillation in hypertensive rats. Am J Hypertens. 2015;28:444–51.CrossRefPubMedGoogle Scholar
  30. 30.
    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.CrossRefPubMedGoogle Scholar
  31. 31.
    Nishihara M, Hirooka Y, Kishi T, Sunagawa K. Different role of oxidative stress in paraventricular nucleus and rostral ventrolateral medulla in cardiovascular regulation in awake spontaneously hypertensive rats. J Hypertens. 2012;30:1758–65.CrossRefPubMedGoogle Scholar
  32. 32.
    Nishihara M, Hirooka Y, Sunagwa K. Combining irebesartan and trichlormethiazide enhances blood pressure reduction via inhibition of sympathetic activity without adverse effects on metabolism in hypertensive rats with metabolic syndrome. Clin Exp Hypertens. 2015;37:33–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Nozoe M, Hirooka Y, Koga Y, Sagara Y, Kishi T, Engelhardt JF, et al. Inhibition of rac1-derived reactive oxygen species in nucleus tractus solitarius decreases blood pressure and heart arte in stroke-prone spontaneously hypertensive rats. Hypertension. 2007;50:62–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Nozoe M, Hirooka Y, Koga Y, Araki S, Konno S, Kishi T, et al. Mitochndria-derived reactive oxygen species mediate sympathoexcitation induced by angiotensin II in the rostral ventrolateral medulla. J Hypertens. 2008;26:2176–84.CrossRefPubMedGoogle Scholar
  35. 35.
    Ogawa K, Hirooka Y, Shinohara K, Kishi T, Sunagawa K. Inhibition of oxidative stress in rostral ventrolateral medulla improves impaired baroreflex sensitivity in stroke-prone spontaneously hypertensive rats. Int Heart J. 2012;53:193–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Shinohara K, Hirooka Y, Kishi T, Sunagawa K. Reduction of nitric oxide-mediated γ-amino butyric acid release in rostral ventrolateral medulla is involved in superoxide-induced sympathoexcitation of hypertensive rats. Circ J. 2012;76:2814–21.CrossRefPubMedGoogle Scholar
  37. 37.
    Sorota S. The sympathetic nervous system as a target for the treatment of hypertension and cardiometabolic diseases. J Cardiovasc Pharamacol. 2014;63:466–76.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Advanced Cardiovascular Regulation and Therapeutics, Center for Disruptive Cardiovascular MedicineKyushu UniversityHigashi-ku, FukuokaJapan
  2. 2.Department of Therapeutic Regulation of Cardiovascular Homeostasis, Center for Disruptive Cardiovascular MedicineKyushu UniversityFukuokaJapan

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