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Role of Rho-kinase within the brain in abnormality of regulation of sympathetic nervous system in hypertension

Research Project

Project/Area Number 13670721
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 Hospital, Department of Cardiovascular Medicine, Assistant Professor, 医学部附属病院, 助手 (90284497)

Co-Investigator(Kenkyū-buntansha) SHIMOKAWA Hiroaki  Kyushu University Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Associate Professor, 大学院・医学研究院, 助教授 (00235681)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsRho / Rho-kinase / brain / blood pressure / sympathetic nervous system / gene transfer / signal transmission / hypertension / 遺伝子導入 / シグナル伝達
Research Abstract

Recent studies have demonstrated that the Rho/Rho-kinase pathway plays an important role in various cellular functions, including actin cytoskeleton organization and vascular smooth muscle contraction. This pathway is also present in the central nervous system, and has been shown to be involved in the maintenance of dendritic spines, in the process of axon outgrowth, and in the regulation of neurotransmitter release. However, its role in central blood pressure regulation is totally unknown. The blockade of the Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem by microinjection of a specific Rho-kinase inhibitor decreased blood pressure, heart rate, and renal sympathetic nerve activity in both Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). However, the magnitude of decreases in these variables was greater in SHR than in WKY. In addition, an adenovirus vector encoding dominant-negative Rho-kinase decreased blood pressure, heart rate, and urinary norepinephrine excretion in both WKY and SHR in the conscious state. The magnitude of decreases in these variables was also greater in SHR than in WKY. Furthermore, expression of RhoA in membrane and the activity of Rho-kinase in the NTS were enhanced in SHR as compared to WKY. These observations indicate that the Rho/Rho-kinase pathway in the NTS contributes to blood pressure regulation via the sympathetic nervous system in vivo, and that activation of this pathway may be involved in the central mechanisms of hypertension.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Kishi T, Hirooka Y, Kimura Y, Sakai K, Ito K, Shimokawa H, Takeshita A.: "Overexpression of eNOS in RVLM improves the impaired baroreflex control of heart rate in SHRSP"Hypertension. 41(2). 255-260 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishi T, Hirooka Y, Mukai Y, Shimokawa H, Takeshita A.: "Atorvastatin causes depressor and sympatho-inhibitory effects with upregulation of nitric oxide synthase in stroke-prone spontaneously hypertensive rats"Journal of Hypertension. 21(2). 379-386 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirooka Y, Kishi T, Shimokawa H, Takeshita A.: "Effects of overproduction of nitric oxide in the brain stem on the cardiovascular response in conscious rats"Journal of Cardiovascular Pharmacology. 41(Suppl.1). S119-S126 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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. 39(2). 264-268 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumoto A, Hirooka Y, et al.: "Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans"Hypertension. 38(6). 1307-1310 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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. 38(4). 896-901 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirooka Y, et al., Edited by Chapleau MW, Abboud F.: "NEURO-CARDIOVASCULAR REGULATION : From Molecules to Man"New York Academy of Sciences. 546 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishi T, Hirooka Y, Kimura Y, Sakai K, Ito K, Shimokawa H, Takeshita A.: "Overexpression of eNOS in RVLM improves the impaired baroreflex control of heart rate in SHRSP."Hypertension.. 41(2). 255-260 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishi T, Hirooka Y, Mukai Y, Shimokawa H, Takeshita A.: "Atorvastatin causes depressor and sympatho-inhibitory effects with upregulation of nitric oxide synthase in stroke-prone spontaneously hypertensive rats."Journal of Hypertension.. 21(2). 379-386 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirooka Y, Kishi T, Sakai K, Shimokawa H, Takeshita A.: "Effect of overproduction of nitric oxide in the brain stem on the cardiovascular response in conscious rats."Journal of Cardiovascular Pharmacology.. 41(Suppl. 1). S119-S126 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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.. 39(2). 264-268 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumoto H, Hirooka Y, Shimokawa H, Hironaga K, Setoguchi S, Takeshita A.: "Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans."Hypertension.. 38(6). 1307-1310 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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.. 38(4). 896-901 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirooka Y, Sakai K, Kishi T, Takeshita A.: "Adenovirus-mediated gene transfer into the NTS in conscious rats: a new approach to examining the central control of cardiovascular regulation. In Neuro-Cardiovascular Regulation, Edited by Abboud FM, and Chapleau M."Annals of the New York Academy of Sciences.. 940. 197-205 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishi T, Hirooka Y, et al.: "Overexpression of eNOS in RVLM improves the impaired baroreflex control of heart rate in SHRSP"Hypertension. 41(2). 255-260 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kishi T, Hirooka Y, et al.: "Overexpression of eNOS in RVLM improves the impaired baroreflex control of heart rate in SHRSP"Journal of Hypertension. 21(2). 379-386 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masumoto A, Hirooka Y, et al.: "Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans"Hypertension. 38(6). 1307-1310 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kishi T, Hirooka Y, et al.: "Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive rats"Hypertension. 39(2). 264-268 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 廣岡良隆, 下川宏明, 竹下 彰: "高血圧の病態におけるRho-kinaseの役割"日本循環器学会専門医誌. 10(2). 303-308 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 廣岡良隆, 下川宏明: "高血圧とRho-kinase"Medical Practice. 19(9). 1523-1526 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirooka Y, et al., Edited by Chapleau MW, Abboud F.: "NEURO-CARDIOVASCULAR REGULATION : From Molecules to Man"New York Academy of Sciences. 546 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masumoto A, Hirooka Y, Shimokawa H, et al.: "Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans"Hypertension. 38. 1307-1310 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kishi T, Hirooka Y, et al.: "Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in SHRSP"Hypertension. 39. 264-268 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kishi T, Hirooka Y, et al.: "Overexpression of eNOS in the RVLM causes hypotension and bradycardia via GABA release"Hypertension. 38. 896-901 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shigematsu H, Hirooka Y, et al.: "Endogenous angiotensin II in the NTS contributes to sympathetic activation in rats with aortocaval shunt"American Journal of Physiology. 280. R1665-R1673 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuo I, Hirooka Y, et al.: "Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo"American Journal of Physiology. 280. R1285-R1291 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Dampney RAL, Coleman MAP, Fontes MAP, Hirooka Y, et al.: "Central mechanisms underlying short-term and long-term regulation of the cardiovascular system"Clinical Experimental Pharmacology and Physiology. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirooka Y, et al., Edited by Chapleau MW, Abboud F.: "NEURO-CARDIOVASCULAR REGULATION : From Molecules to Man"New York Academy of Sciences. 546 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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