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Role of reactive oxygen species within the vasomotor center of the brain in hypertension

Research Project

Project/Area Number15590757
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

HIROOKA Yoshitaka  Kyushu University, Coronary Care Unit, Kyushu University Hospital, Assistant Professor, 大学病院, 講師 (90284497)

Co-Investigator(Kenkyū-buntansha) SHIMOKAWA Hiroaki  Kyushu University, Department of Clinical Medicine, Faculty of Medicine, Associate professor, 大学院・医学研究院, 助教授 (00235681)
Project Period (FY) 2003 – 2004
Project Status Completed(Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2004 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 2003 : ¥2,200,000 (Direct Cost : ¥2,200,000)
KeywordsReactive oxygen species / blood pressure / heart rate / sympathetic nervous system / gene / brain / nitric oxide / norepinephrine / 交感神経系 / 酸化ストレス / 高血圧
Research Abstract

Oxidative stress increases in hypertension. The aim of this study was to determine whether reactive oxygen species(ROS) are increased in the rostral ventrolateral medulla(RVLM) in the brainstem, where the vasomotor center is located, in stroke-prone spontaneously hypertensive rats(SHRSP), and, if so, to determine whether the increased ROS contribute to neural mechanisms of hypertension in SHRSP. We measured ROS levels in the RVLM of SHRSP and compared them with those in Wistar-Kyoto rats(WKY). Thiobarbituric acid-reactive substances were increased in SHRSP compared with WKY. ROS were also measured by electron spin resonance(ESR) spectroscopy. The ESR signal decay rate in the RVLM of SHRSP was significantly increased compared with that in WKY, and this increase was abolished by dimethylthiourea (a hydroxyl radical scavenger). The increased ESR signal decay was reduced to the same extent in the presence of desferrioxamine, catalase, and Tiron, indicating that hydroxyl radicals are derived from superoxide anions and hydrogen peroxide. In addition, total superoxide dismutase(SOD) activity in the RVLM decreased blood pressure in SHRSP but not in WKY, and MnSOD overexpression in the RVLM of SHRSP decreased blood pressure and inhibited sympathetic nerve activity. These results suggest that superoxide anions in the RVLM, which generate hydroxyl radicals, are increased in SHRSP and contribute to the neural mechanisms of hypertension in SHRSP. We also examined the role of inducible nitric oxide synthase(iNOS) in the RVLM in the control of blood pressure and sympathetic nerve activity. We fond that overexpression of iNOS in the RVLM increases blood pressure via activation of the sympathetic nervous system, which is mediated by an increase in oxidative stress.

Report

(3results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report

Research Products

(19results)

All 2005 2004 2003 Other

All Journal Article Book Publications

  • [Journal Article] Overexpression of inducible nitric oxide synthase in rostral ventrolateral medulla causes hypertension and sympathoexcitation via an increase in oxidative stress.2005

    • Author(s)
      Kimura Y, Hirooka Y et al.
    • Journal Title

      Circulation Research 96

      Pages : 252-260

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Overexpression of inducible nitric oxide synthase in rostral ventrolateral medulla causes hypertension and sympathoexcitation via an increase hi oxidative stress.2005

    • Author(s)
      Kimura Y, Hirooka Y et al.
    • Journal Title

      Circulation Research 96

      Pages : 252-260

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rho/Rho-kinase pathway in the brainstem contributes to hypertension caused by chronic nitric oxide synthase inhibition.2004

    • Author(s)
      Ito K, Hirooka Y et al.
    • Journal Title

      Hypertension 43

      Pages : 156-162

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats.2004

    • Author(s)
      Kishi T, Hirooka Y et al.
    • Journal Title

      Circulation 109

      Pages : 2357-2362

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated gene transfer into the brain stem to examine cardiovascular function : Role of nitric oxide and Rho-kinase.2004

    • Author(s)
      Hirooka Y
    • Journal Title

      Progress in Biophysics and Molecular Biology 84

      Pages : 233-249

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of Rho-kinase in the brainstem augments baroreflex control of heart rate in rats.2004

    • Author(s)
      Ito K, Hirooka Y et al.
    • Journal Title

      Hypertension 44

      Pages : 478-483

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated gene transfer into the brain stem to examine cardiovascular function : Role of nitric oxide and Rho-kinase.2004

    • Author(s)
      Hirooka Y.
    • Journal Title

      Progress in Biophysics and Molecular Biology 84

      Pages : 233-249

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated nitric oxide synthase gene transfer into the nucleus tractus solitarius in conscious rats.2004

    • Author(s)
      Hirooka Y, Sakai K.
    • Journal Title

      Methods in Molecular Biology 279

      Pages : 187-200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated gene transfer into the brain stem to examine cardiovascular function : Role of nitric oxide and Rhokinase.2004

    • Author(s)
      Hirooka Y
    • Journal Title

      Progress in Biophysics and Molecular Biology 84

      Pages : 23-249

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Rho/Rho-kinase pathway in brain stem contributes to blood pressure regulation via sympathetic nervous system : possible involvement in neural mechanisms of hypertension.2003

    • Author(s)
      Ito K, Hirooka Y et al.
    • Journal Title

      Circulation Research 92

      Pages : 1337-1343

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Book] Methods in Molecular Biology2004

    • Author(s)
      Hirooka Y, Sakai K.
    • Total Pages
      14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Methods in Molecular Biology2004

    • Author(s)
      Hirooka Y, Sakai K.
    • Total Pages
      14
    • Related Report
      2004 Annual Research Report
  • [Publications] 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. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 廣岡良隆, 下川宏明: "高血圧と酸化ストレス"臨床高血圧. 9. 18-25 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirooka Y: "Adenovirus-mediated gene transfer into the brain stem to examine cardiovascular function : role of nitric oxide and Rho-kinase."Progress in Biophysics & Molecular Biology. 84. 233-249 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito K, Hirooka Y, Kishi T, Kimura Y, Kaibuchi K, Shimokawa H, Takeshita A: "Rho/Rho-kinase pathway in the brainstem contributes to hyperetnsion caused by chronic nitric oxide synthase inhibition."Hypertension. 43. 156-162 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito K, Hirooka Y, Sakai K, Kishi T, Kaibuchi K, Shimokawa H, Takeshita A: "Rho/Rho-kinase pathway in brain stem contributes to blood pressure regulation via sympathetic nervous system : possible involvement in neural mechanisms of hypertension."Circulation Research. 92. 1337-1343 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirooka Y, Sakai K, Kishi T, Ito K, Shimokawa H, Takeshita A: "Enhanced depressor response to endothelial nitric oxide synthase gene transfer into the nucleus tractus solitarii of spontaneously hypertensive rats."Hypertension Research. 26. 325-331 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirooka Y, Sakai K: "Nitric Oxide Protocols"Humana Press (In press). (2004)

    • Related Report
      2003 Annual Research Report

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Published : 2003-04-01   Modified : 2016-04-21  

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