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Examination of the mechanism of the stress inhibitor on the brain-cardio-renal syndrome.

Research Project

Project/Area Number 20K07300
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48030:Pharmacology-related
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

Nakata Tetsuo  京都薬科大学, 薬学部, 教授 (30237292)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsストレス / 高血圧 / 交感神経 / レニンアンギオテンシン系 / 脳心腎連関 / 脳微小灌流法 / 交感神経活性 / 当帰 / 視床下部 / トウキ葉 / リグスチリド / GABA / α-リノレン酸 / 自律神経活動 / 食塩負荷高血圧 / 脳微量灌流法 / αリノレン酸 / ストレス負荷 / ストレス耐性 / 交感神経活動 / 脳微小還流法 / 脳腸連関
Outline of Research at the Start

熊本地震によるストレスで高血圧が3.4%、糖尿病が2.5%急増したと健保調査が伝えている。ストレスによる昇圧反応には交感神経活動の亢進が考えられるが、個人差が大きいと言われる。ストレス耐性効果のある自然由来物質はいくつかあげられるが、その効果の定量化と機序の詳細な検討は行われていない。今回、病態モデルラットに脳微小透析法を用い、振盪(shaker)ストレス負荷時の心血管反応、自律神経の揺らぎ解析とリアルタイムな中枢神経伝達物質であるGABA、glutamate、一酸化窒素の動態を検討し、α-リノレン酸、当帰、GABA投与によるshakerストレス耐性効果およびその機序について明らかにする。

Outline of Final Research Achievements

It has been reported that α-linolenic acid and Toki extract have the effect of suppressing the development of hypertension and suppressing the pressor response during stress. Suppression of sympathetic nerve activity and inhibitory effects on the renin-angiotensin system have been suggested as the mechanism, but the details of the involvement of neurotransmitters in the brain during wakefulness are unknown. Therefore, in this study, we used cerebral microperfusion to examine the relationship between cardiovascular responses and neurotransmitters in the brain during stress. We have previously reported that noradrenaline and nitric oxide (NO) in the hypothalamic paraventricular nucleus (PVN) are related to stress responses. Here, we focused on the cardiovascular response to Air Jet stress and the dynamics of NO in PVN.

Academic Significance and Societal Importance of the Research Achievements

高血圧をはじめとする循環器疾患のリスクの1つに「ストレス」があることが知られている。最近ではスマートフォンやapple watchを用いて簡便に心拍間隔の変動から副交感神経の活動度を表示し、リラックス度として利用するソフトも散見される。ストレス社会において、よりストレス反応を抑制(ストレスによる脳心血管イベントを抑制する)物質が望まれる。更に、現代の健康志向社会から、自然食品の中からそのような効果を示すものを見出し、その機序を科学的に諸王明することが必要と考えられる。我々は既に、降圧、ストレス耐性を示す天然由来・食品成分の候補を探索してきた。今回その機序について検討した。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (28 results)

All 2023 2022 2021 2020

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 9 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] Eicosapentaenoic Acid Preserves Mitochondrial Quality and Attenuates Cardiac Remodeling After Myocardial Infarction in Rats2023

    • Author(s)
      Kobara Miyuki、Shiraishi Tatsuya、Noda Kazuki、Toba Hiroe、Nakata Tetsuo
    • Journal Title

      Journal of Cardiovascular Translational Research

      Volume: 27 Issue: 4 Pages: 816-827

    • DOI

      10.1007/s12265-023-10363-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nicorandil Suppresses Ischemia-Induced Norepinephrine Release and Ventricular Arrhythmias in Hypertrophic Hearts2022

    • Author(s)
      Kobara Miyuki、Amano Toshihiro、Toba Hiroe、Nakata Tetsuo
    • Journal Title

      Cardiovascular Drugs and Therapy

      Volume: 37 Issue: 1 Pages: 53-62

    • DOI

      10.1007/s10557-022-07369-1

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Secreted protein acidic and rich in cysteine (SPARC) and a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) increments by the renin-angiotensin system induce renal fibrosis in deoxycorticosterone acetate-salt hypertensive rats2022

    • Author(s)
      Toba Hiroe、Ikemoto Mitsushi J.、Kobara Miyuki、Nakata Tetsuo
    • Journal Title

      European Journal of Pharmacology

      Volume: 914 Pages: 174681-174681

    • DOI

      10.1016/j.ejphar.2021.174681

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angelica acutiloba Exerts Antihypertensive Effect and Improves Insulin Resistance in Spontaneously Hypertensive Rats Fed with a High-Fat Diet2022

    • Author(s)
      Watanabe Yusuke、Nessa Naseratun、Toba Hiroe、Kobara Miyuki、Nakata Tetsuo
    • Journal Title

      Pharmacology

      Volume: 107 Issue: 3-4 Pages: 188-196

    • DOI

      10.1159/000520982

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of autophagy in angiotensin II-induced cardiomyocyte apoptosis2022

    • Author(s)
      Miyuki Kobara, Hiroe Toba, Tetsuo Nakata
    • Journal Title

      Clin Exp Pharmacol Physiol.

      Volume: 49 Issue: 12 Pages: 1342-1351

    • DOI

      10.1111/1440-1681.13719

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Raman Metabolomics of Candida auris Clades: Profiling and Barcode Identification2022

    • Author(s)
      Pezzotti Giuseppe、Kobara Miyuki、Nakaya Tamaki、Imamura Hayata、Fujii Tomoya、Miyamoto Nao、Adachi Tetsuya、Yamamoto Toshiro、Kanamura Narisato、Ohgitani Eriko、Marin Elia、Zhu Wenliang、Kawai Toshihisa、Mazda Osam、Nakata Tetsuo、Makimura Koichi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 19 Pages: 11736-11736

    • DOI

      10.3390/ijms231911736

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Raman Spectroscopy of Oral Candida Species: Molecular-Scale Analyses, Chemometrics, and Barcode Identification2022

    • Author(s)
      Pezzotti Giuseppe、Kobara Miyuki、Nakaya Tamaki、Imamura Hayata、Miyamoto Nao、Adachi Tetsuya、Yamamoto Toshiro、Kanamura Narisato、Ohgitani Eriko、Marin Elia、Zhu Wenliang、Nishimura Ichiro、Mazda Osam、Nakata Tetsuo、Makimura Koichi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 10 Pages: 5359-5359

    • DOI

      10.3390/ijms23105359

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Raman Study of Pathogenic Candida auris: Imaging Metabolic Machineries in Reaction to Antifungal Drugs2022

    • Author(s)
      Pezzotti Giuseppe、Kobara Miyuki、Nakaya Tamaki、Imamura Hayata、Asai Tenma、Miyamoto Nao、Adachi Tetsuya、Yamamoto Toshiro、Kanamura Narisato、Ohgitani Eriko、Marin Elia、Zhu Wenliang、Nishimura Ichiro、Mazda Osam、Nakata Tetsuo、Makimura Koichi
    • Journal Title

      Frontiers in Microbiology

      Volume: 13 Pages: 11736-11736

    • DOI

      10.3389/fmicb.2022.896359

    • URL

      https://pure.teikyo.jp/en/publications/746b8ef5-2a6f-435f-9fd2-7ab14ba6a487

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preconditioning with Short-Term Dietary Restriction Attenuates Cardiac Oxidative Stress and Hypertrophy Induced by Chronic Pressure Overload2021

    • Author(s)
      Miyuki Kobara,Nessa Naseratun,Hiroe Toba andTetsuo Nakata
    • Journal Title

      Nutrients

      Volume: 13 Issue: 3 Pages: 737-737

    • DOI

      10.3390/nu13030737

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Febuxostat Attenuates the Progression of Periodontitis in Rats2021

    • Author(s)
      Naseratun Nessa 1, Miyuki Kobara , Hiroe Toba , Tetsuya Adachi , Toshiro Yamamoto , Narisato Kanamura , Giuseppe Pezzotti , Tetsuo Nakata
    • Journal Title

      Pharmacology

      Volume: 18 Issue: 5-6 Pages: 1-11

    • DOI

      10.1159/000513034

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Induction of autophagy has protective roles in imatinib-induced cardiotoxicity.2021

    • Author(s)
      Kobara Miyuki, Naseratun Nessa, Toba Hiroe, Nakata Tetsuo.
    • Journal Title

      Toxicology Reports

      Volume: 8 Pages: 1087-1097

    • DOI

      10.1016/j.toxrep.2021.05.008

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Raman Imaging of Pathogenic Candida auris: Visualization of Structural Characteristics and Machine-Learning Identification2021

    • Author(s)
      Pezzotti Giuseppe, Kobara Miyuki, Nakata Tetsuo, et al.
    • Journal Title

      Front Microbiol

      Volume: 12

    • DOI

      10.3389/fmicb.2021.769597

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of effects of L/N-type and L-type calcium channel blockers on post-infarct cardiac remodelling in spontaneously hypertensive rats2020

    • Author(s)
      Nessa Naseratun, Miyuki Kobara, Yusuke Watanabe, Hiroe Toba, Tetsuo Nakata
    • Journal Title

      Clin Exp Pharmacol Physiol .

      Volume: 47 Issue: 9 Pages: 1545-1553

    • DOI

      10.1111/1440-1681.13329

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 虚血誘導性心筋内ノルエピネフリン放出及び虚血性心室性不整脈に対するニコランジルの影響2023

    • Author(s)
      小原 幸, 鳥羽裕恵, 中田徹男
    • Organizer
      第32回日本循環薬理学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 細胞外マトリックスSPARCは炎症を惹起し高血圧性血管障害の原因となる2023

    • Author(s)
      坂元聡太, 鳥羽 裕恵, 小原 幸, 中田 徹男
    • Organizer
      第52回日本心脈管作動物質学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Roles of angiotensin II-induced autophagy in mitochondrial injury and apoptosis in cardiomyocytes2023

    • Author(s)
      Miyuki Kobara, Hiroe Toba, Tetsuo Nakata
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] GLP-1 analogue suppresses hyperglycemia-induced podocyte injury via akt-bcl2 preservation2023

    • Author(s)
      Miyuki Kobara, Hiroe Toba, Tetsuo Nakata
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Low dose of erythropoietin attenuates insulin resistance, renal fibrosis, and vascular inflammation in sucrose-treated rats2023

    • Author(s)
      Hiroe Toba, Miyuki Kobara, Tetsuo Nakata
    • Organizer
      第87回日本循環器学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] インスリン抵抗性モデルラットの耐糖能異常と臓器障害に対するエリスロポエチンの効果の検討2023

    • Author(s)
      瀧澤恭平, 鳥羽 裕恵, 小原 幸, 中田 徹男
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 高血圧性血管障害における細胞外マトリックスSPARCの役割の検討2023

    • Author(s)
      坂元聡太, 鳥羽 裕恵, 小原 幸, 中田 徹男
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] アンジオテンシンII誘発性オートファジーの心筋細胞アポトーシスに対する影響2022

    • Author(s)
      小原 幸, 鳥羽裕恵, 中田徹男
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 血管内皮機能障害時における細胞外マトリックスSPARCの役割の検討2022

    • Author(s)
      鳥羽 裕恵、小原 幸、中田 徹男
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Honokiol Preserves Mitochondrial Sirtuin 3 And Attenuates Hypoxia-reoxygenation Injury in Cultured Myocytes2022

    • Author(s)
      Kobara M, Toba H, Nakata T
    • Organizer
      第86回日本循環器学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ドラッグリポジショニングを用いた歯周炎の予防2021

    • Author(s)
      小原 幸, 鳥羽裕恵, 中田徹男
    • Organizer
      第21回日本抗加齢医学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Expression and roles of N-type Ca channel in cardiomyocytes2021

    • Author(s)
      Kobara Miyuki, Toba Hiroe, Nakata Tetsuo
    • Organizer
      欧州心臓学会,(バーチャル開催)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Anti-inflammatory and anti-oxidative effects of febuxostat on periodontitis rats model2021

    • Author(s)
      Naseratun Nessa, Kobara Miyuki, Adachi Tetsuya, Yamamoto Toshiro, Nakata Tetsuo, Kanamura Narisato
    • Organizer
      第69回国際歯科研究学会日本部会総会・学術大会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of oxidative stress by dietary and pharmacological interventions in heart failure2021

    • Author(s)
      Kobara Miyuki, Toba Hiroe, Nakata
    • Organizer
      ESMED Congress
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 培養糸球体足細胞における高血糖障害に対するGLP-1受容体作動薬の効果2021

    • Author(s)
      宮石和恭, 小原 幸, 小西巧真, 鈴木佑実, 宮川真由香, 鳥羽裕恵, 中田徹男
    • Organizer
      ,第31回日本循環薬理学会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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