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Salt-sensitive hypertension and vascular dysfunction

Research Project

Project/Area Number 17K09724
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionInternational University of Health and Welfare

Principal Investigator

Shimosawa Tatsuo  国際医療福祉大学, 医学部, 主任教授 (90231365)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords食塩感受性高血圧 / 血管内皮機能 / 遠位尿細管 / ナトリウム / 酸化ストレス / Na-Cl共輸送体 / 一酸化窒素 / 内科 / 高血圧 / 血管
Outline of Final Research Achievements

To investigate the cause of salt sensitivity, we used low-dose L-NAME. A high salt diet increased the circulating blood volume regardless of the L-NAME-treatment for the first 24 hours but it returned to the baseline in nontreated group. In contrast to the blood volume changes, blood pressure was higher only in the L-NAME-treated group. An increase in natriuresis was observed after treatment with hydrochlorothiazide, but not amiloride, and this change was observed in parallel with increases in phosphorylated NCC. A change in blood pressure was not observed in the L-NAME-treated NCC-deficient mice fed a high salt diet. Moreover, L-NAME-induced NCC activation was demonstrated in mDCT cells. The effect of L-NAME on phosphorylated NCC was blocked by both the SPAK inhibitor and TEMPO. TEMPO also attenuated salt-induced hypertension. In conclusion, even slightly impaired NO may be important in salt sensitivity.

Academic Significance and Societal Importance of the Research Achievements

高齢者、糖尿病、動脈硬化疾患など食塩感受性を呈しやすい病態に血管拡張機能低下が関与することを示唆するものである。
予後不良の食塩感受性高血圧の治療には腎臓ならびに酸化ストレス、血管反応性を考慮することが必要である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (10 results)

All 2020 2019 2018 2017

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] In rodents, low dose L-NAME induces salt sensitivity in association with sustained increases in blood volume and in activity of the Na+-Cl- cotransporter (NCC)2020

    • Author(s)
      Conghui Wang, Fumiko Kawakami-Mori, Lei Kang, Nobuhiro Ayuzawa, Sayoko Ogura, Suang Suang Koid, Latapati Reheman, Alimila Yeerbolati2 Beibei Liu, Yutaka Yatomi, Xiangmei Chen, Toshiro Fujita, Tatsuo Shimosawa
    • Journal Title

      Kidney International

      Volume: in press Pages: 0-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 血管内皮機能の低下と食洗感受性高血圧.2019

    • Author(s)
      下澤達雄
    • Organizer
      第42回日本基礎老化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MR活性にかかわる因子基礎的検討から2019

    • Author(s)
      下澤達雄
    • Organizer
      第42回日本高血圧学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] The mechanism of Salt sensitive Hypertension in Intermittent Hypoxia.2018

    • Author(s)
      Alimila Yeerbolati, Sayoko Ogura, Latapati Reheman, Conghui Wang, Beibei Liu, Ichiro Kuwahira, Mikiyasu Shirai, Tatsuo Shimosawa, Toshiro Fujita.
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Low dose N nitro arginine methyl ester( NAME) causes salt sensitive hypertension via activation of Na+Cl cotransporter(NCC)2018

    • Author(s)
      Wang C, Shimosawa T, Koid S S, Ogura S, Reheman L.
    • Organizer
      The 27th Scientific meeting of the International Society of Hypertension
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Oxidative stress causes salt sensitive hypertension via activation of Na+-Cl-cotransporter(ncc).2018

    • Author(s)
      Wang C, Shimosawa T, Reheman L, Koid S S, Yeerbolati A, Liu B, Mori F, Fujita T.
    • Organizer
      Joint Hypertension Scientific Sessions of American Heart Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Low dose L‐NAME causes salt sensitive hypertension via activation of NCC.2017

    • Author(s)
      Conghui Wang, Sayoko Ogura, Fumiko Mori, Suang Koid, Alimila Yeerbolati, Latapati Reheman, Beibei Liu, Tatsuo Shimosawa.
    • Organizer
      Joint Hypertension 2017 Scientific Session/AHA Council on Hypertension/AHA Council on Kidney in Cardiovascular Disease/American Society of Hypertension,
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Low Dose N-nitro-L-arginide Methyl Ester (L‐NAME) Causes Salt Sensitive Hypertension via Activation of Na+-Cl-Cotrasporter (NCC).2017

    • Author(s)
      Conghui Wang, Latapati Reheman, Sayoko Ogura, Suang Suang Koid, Fumiko Mori, Tatsuo Shimosawa.
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Low dose L‐NAME causes salt sensitive hypertension via activation of NCC.2017

    • Author(s)
      Conghui Wang, Sayoko Ogura, Fumiko Mori, Suang Koid, Alimila Yeerbolati, Latapati Reheman, Beibei Liu, Tatsuo Shimosawa.
    • Organizer
      第34回国際心臓研究学会日本部会,
    • Related Report
      2017 Research-status Report
  • [Book] Hypertensive Target Organ Damage:Mechanism and Recognition2019

    • Author(s)
      Shimosawa T
    • Total Pages
      398
    • Publisher
      Jaypee Brothers Medical Publishers
    • ISBN
      9789386261489
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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