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Role of microvascular dysfunction in the cardiovascular center for development of hypertension

Research Project

Project/Area Number 26670413
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Shirai Mikiyasu  国立研究開発法人国立循環器病研究センター, 研究所, 部長 (70162758)

Co-Investigator(Kenkyū-buntansha) TSUCHIMOCHI HIROTSUGU  国立研究開発法人国立循環器病研究センター, 研究所, 室長 (60379948)
Co-Investigator(Renkei-kenkyūsha) INAGAKI TADAKATSU  国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (20638366)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords高血圧 / 交感神経活動 / 心臓血管中枢 / 延髄微小循環 / 高血圧自然発症ラット / 間歇的低酸素 / 肺循環 / 循環器・高血圧 / 肺交感神経活動 / 微小循環
Outline of Final Research Achievements

We applied synchrotron radiation microangiography to young (4-week-old) spontaneously hypertensive rat (SHR) whose blood pressure is usually normal and found that arterioles in the medulla oblongata show abnormal responses (vasoconstriction) specifically with acute hypoxic exposure. In the unanesthetized young SHR, we measured renal and lumbar sympathetic nerve activity (SNA) for a month and found no significant SNA increase despite progressive rise in systemic blood pressure. In the chronic intermittent hypoxic rat, the SNA increased in proportion to blood pressure rise, but pulmonary SNA increase is not accompanied by pulmonary pressor response during acute hypoxic exposure. The inhibition of SNA increase with central β1 receptor blockade disclosed the hypoxic pulmonary pressor response, suggesting the SNA increase attenuates the hypoxic pulmonary response. These data suggest an important role of the ischemic state of the cardiovascular center for controlling SNA and blood pressure.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (19 results)

All 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 5 results)

  • [Int'l Joint Research] Dept. of Physiology, Monash University(Australia)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Dept. of Physiology, Otago University(New Zealand)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia2015

    • Author(s)
      Hisashi Nagai, Ichiro Kuwahira, Daryl O. Schwenke, Hirotsugu Tsuchimochi, Akina Nara, Sayoko Ogura, Takashi Sonobe, Tadakatsu Inagaki, Yutaka Fujii, Rutsuko Yamaguchi, Lisa Wingenfeld, Keiji Umetani, Tatsuo Shimosawa, Kenichi Yoshida, Koichi Uemura, James T. Pearson, Mikiyasu Shirai
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 7 Pages: 1-20

    • DOI

      10.1371/journal.pone.0131923

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ghrelin supresses sympathetic hyper-excitation in acute heart failure in male rats - assessing centrally and peripherally mediated pathways2015

    • Author(s)
      Shirai M, Joe N, Tsuchimochi H, Sonobe T, Schwenke DO.
    • Journal Title

      Endocrinology

      Volume: 156 Issue: 9 Pages: 3309-3316

    • DOI

      10.1210/en.2015-1333

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Guanfacine enhances cardiac acetylcholine release with little effect on norepinephrine release in anesthetized rabbits.2015

    • Author(s)
      Shimizu S, Kawada T, Akiyama T, Turner MJ, Shishido T, Kamiya A, Shirai M, Sugimachi M.
    • Journal Title

      Autonomic Neuroscience

      Volume: 187 Pages: 84-87

    • DOI

      10.1016/j.autneu.2014.11.010

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] readmill running improves hindlimb arteriolar endothelial function in type 1 diabetic mice as visualized by X-ray microangiography.2015

    • Author(s)
      Sonobe T, Tsuchimochi H, Schwenke DO, Pearson JT, Shirai M.
    • Journal Title

      Cardiovasc Diabetol

      Volume: 13 Issue: 1

    • DOI

      10.1186/s12933-015-0217-0

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Interleukin-6/interleukin-21 signaling axis is critical in the pathogenesis of pulmonary arterial hypertension2015

    • Author(s)
      Hashimoto-Kataoka T, Hosen N, Sonobe T, Arita Y, Yasui T, Masaki T, Minami M, Inagaki T, Miyagawa S, Sawa Y, Murakami M, Kumanogoh A, Yamauchi-Takihara K, Okumura M, Kishimoto T, Komuro I, Shirai M, Sakata Y, and Nakaoka Y
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: Early Edition Issue: 20 Pages: 1-10

    • DOI

      10.1073/pnas.1424774112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] APJ Regulates Parallel Alignment of Arteries and Veins in the Skin.2015

    • Author(s)
      Kidoya H, Naito H, Muramatsu F, Yamakawa D, Jia W, Ikawa M, Sonobe T, Tsuchimochi H, Shirai M, Adams RH, Fukamizu A, Takakura N.
    • Journal Title

      Dev Cell.

      Volume: 33 Issue: 3 Pages: 247-259

    • DOI

      10.1016/j.devcel.2015.02.024

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chronic Rho-kinase inhibition improves left ventricular contractile dysfunction in early type-1 diabetes by increasing myosin cross-bridge extension.2015

    • Author(s)
      Waddingham MT, Edgley AJ, Astolfo A, Inagaki T, Fujii Y, Du CK, Zhan DY, Tsuchimochi H, Yagi N, Kelly DJ, Shirai M, Pearson JT.
    • Journal Title

      Cardiovasc Diabetol

      Volume: 14 Issue: 1 Pages: 92-105

    • DOI

      10.1186/s12933-015-0256-6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pulmonary vascular tone is dependent on the central modulation of sympathetic nerve activity following chronic intermittent hypoxia2014

    • Author(s)
      Mikiyasu Shirai, Hirotsugu Tsuchimochi, Hisashi Nagai, Emily Gray, James Todd Pearson, Takashi Sonobe, Misa Yoshimoto, Tadakatsu Inagaki, Yutaka Fujii, Keiji Umetani, Ichiro Kuwahira, Daryl Schwenke
    • Journal Title

      Basic Research in Cardiology

      Volume: 109 Issue: 5 Pages: 432-432

    • DOI

      10.1007/s00395-014-0432-y

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Beta2-adrenergic receptor-dependent attenuation of hypoxic pulmonary vasoconstriction prevents progression of pulmonary arterial hypertension in intermittent hypoxic rats2014

    • Author(s)
      Hisashi Nagai, Ichiro Kuwahira, Daryl O. Schwenke, Hirotsugu Tsuchimochi, Akina Nara, Tadakatsu Inagaki, Sayoko Ogura, Yutaka Fujii, Keiji Umetani, Tatsuo Shimosawa, Kenichi Yoshida, James T. Pearson, Koichi Uemura, Mikiyasu Shirai
    • Journal Title

      PLOS ONE

      Volume: 10 Issue: 10 Pages: 1-10

    • DOI

      10.1371/journal.pone.0110693

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute effects of arterial baroreflex on sympathetic nerve activity and plasma norepinephrine concentration.2014

    • Author(s)
      Kawada T, Akiyama T, Shimizu S, Sata Y, Turner MJ, Shirai M, Sugimachi M.
    • Journal Title

      Auton Neurosci

      Volume: 186 Pages: 62-68

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Exercise training attenuates the development of diabetic cardiomyopathy through modulating inflammation and oxidative stress2016

    • Author(s)
      Sukumaran V, Inagaki T, Tsuchimochi H, Shirai M.
    • Organizer
      The 93rd Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Sapporo
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sympathetic hyper-excitation in obesity and pulmonary hypertension; relevance to the Obesity Paradox2016

    • Author(s)
      Schwenke D, Diong C, Shirai M.
    • Organizer
      The 93rd Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Sapporo
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chronic intermittent hypoxia accelerates coronary microcirculatory dysfunction in young insulin resistant Goto-Kakizaki rats.2016

    • Author(s)
      Perason J, Chen Y, Inagaki T, Fujii, Y, Schwenke D, Edgley A, Umetani K, Zhan Y, Yoshimoto M, Tsuchimochi H, Nagai H, Kuwahira I, Evans R, Shirai M.
    • Organizer
      The 93rd Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Sapporo
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fluorescence imaging guided identification of autonomic nerve fibers and the measurement of their activities in vivo by using Thy1-YFP transgenic mice.2016

    • Author(s)
      Tsuchimochi H, Inagaki T, Shirai M.
    • Organizer
      The 93rd Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Sapporo
    • Year and Date
      2016-03-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Critical protective role of endogenous nitric oxide in established severe pulmonary arterial hypertension in rats.2015

    • Author(s)
      Tanaka M, Abe K, Oka M, Schwenke DO, Shirai M, Kuwahira I, Hirooka Y, Hoka S, Sunagawa K.
    • Organizer
      American Heart Association scientific session
    • Place of Presentation
      Florida
    • Year and Date
      2015-11-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effect of blood contact surface area reduction during extracorporeal circulation in a rat cardiopulmonary bypass model.2015

    • Author(s)
      Fujii Y, Shirai M, Takewa Y, Taenaka Y, Tatsumi E
    • Organizer
      American Society for Artificial Internal Organs 61th Annual Conference
    • Place of Presentation
      Chicago
    • Year and Date
      2015-06-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ghrelin acts directly on the CNS to suppress cardiac sympathetic tone and arrhythmias following acute myocardial infarction in rats2015

    • Author(s)
      Shirai M, Joe N, Tsuchimochi H, Schwenke DO
    • Organizer
      92th Annual Meeting of Japan Physiological Society
    • Place of Presentation
      Kobe International Conference Center
    • Year and Date
      2015-03-21
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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