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Basic research on the role of the nitric oxide synthase system in organ connection

Research Project

Project/Area Number 23590305
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionUniversity of the Ryukyus

Principal Investigator

TSUTSUI Masato  琉球大学, 医学(系)研究科(研究院), 教授 (70309962)

Co-Investigator(Renkei-kenkyūsha) NOGUCHI Katsuhiko  琉球大学, 大学院医学研究科, 准教授 (70156181)
MATSUZAKI Toshihiro  琉球大学, 大学院医学研究科, 助教 (50244330)
SAKANASHI Mayuko  琉球大学, 大学院医学研究科, 助教 (80363662)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords一酸化窒素合成酵素 / 臓器連関 / ノックアウトマウス / 一酸化窒素 / 動脈硬化 / 慢性腎臓病 / マウス / 骨髄前駆細胞 / 急性心筋梗塞 / 遺伝子改変マウス
Research Abstract

In order to examine the role of the nitric oxide synthases (NOSs) system in vivo, we generated mice in which all three NOS genes are completely disrupted. In this study, we examined the role of the NOSs system in organ connection by using our triple NOSs-KO mice, and clarified that the NOSs system expressed in bone-marrow-derived vascular smooth muscle progenitor cells exerts an inhibitory effect on vascular lesion formation after carotid artery ligation, and that the NOS system plays a role in reno-cardiac connection.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (34 results)

All 2014 2013 2012 2011 Other

All Journal Article (21 results) (of which Peer Reviewed: 20 results) Presentation (11 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] Plasma levels of nitric oxide metabolites are markedly reduced in normotensive males with electrocardiographically determined left ventricular hypertrophy2014

    • Author(s)
      Kamezaki F, Tsutsui M, Takahashi M, Sonoda S, Kubo T, Fujino Y, Adachi T, Abe H, Takeuchi M, Mayumi T, Otsuji Y
    • Journal Title

      Hypertension

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Selective Estrogen Receptor Modulators on Plasma Membrane Estrogen Receptors and Catecholamine Synthesis and Secretion in Cultured Bovine Adrenal Medullary Cells2014

    • Author(s)
      Inagaki H., Toyohira Y., Takahashi K., Ueno S., Obara G, Kawagoe T., Tsutsui M., Hachisuga T., Yanagihara N
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 124 Issue: 1 Pages: 66-75

    • DOI

      10.1254/jphs.13155FP

    • NAID

      130003382627

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stimulatory effect of nobiletin, a citrus polymethoxy flavone, on catecholamine synthesis through Ser19 and Ser40 phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells2014

    • Author(s)
      Zhang H., Yanagihara N., Toyohira Y., Takahashi K., Inagaki H., Li X., Tsutsui M., Takahashi K
    • Journal Title

      Naunyn-Schmiedeberg’s Arch of Pharmacol

      Volume: 387 Issue: 1 Pages: 15-22

    • DOI

      10.1007/s00210-013-0916-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Nitric oxide mediates selective degeneration of hypothalamic orexin neurons through dysfunction of protein disulfide isomerase.2013

    • Author(s)
      Obukuro K, Nobunaga M, Takigawa M, Morioka H, Hisatsune A, Isohama Y, Shimokawa H, Tsutsui M, Katsuki H.
    • Journal Title

      J Neurosci.

      Volume: 33(31) Issue: 31 Pages: 12557-68

    • DOI

      10.1523/jneurosci.0595-13.2013

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-Term Treatment With San’o-Shashin-To, a Kampo Medicine, Markedly Ameliorates Cardiac Ischemia-Reperfusion Injury in Ovariectomized Rats via the Redox-Dependent Mechanism2013

    • Author(s)
      Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Sakanashi M, Uchida T, Kina-Tanada M, Kubota H, Arakaki K, Tanimoto A, Yanagihara N, Sakanashi M, Ohya Y, Masuzaki H, Ishiuchi S, Sugahara K, Tsutsui M
    • Journal Title

      Circulation Journal

      Volume: 77 Issue: 7 Pages: 1827-1837

    • DOI

      10.1253/circj.CJ-12-1434

    • NAID

      10031173765

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Na(+)/H(+) exchanger inhibitor induces vasorelaxation through nitric oxide production in endothelial cells via intracellular acidification-associated Ca2(+) mobilization.2013

    • Author(s)
      Sasahara T, Yayama K, Matsuzaki T, Tsutsui M, Okamoto H.
    • Journal Title

      Vascu Pharmacol

      Volume: 58(4) Issue: 4 Pages: 319-325

    • DOI

      10.1016/j.vph.2012.11.004

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pentazocine Inhibits Norepinephrine Transporter Function by Reducing its Surface Expression in Bovine Adrenal Medullary Cells2013

    • Author(s)
      Obara G., Toyohira Y., Inagaki H., Takahashi K., Horishita T., Ueno S., Tsutsui M., Yanagihara N
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 121 Issue: 2 Pages: 138-147

    • DOI

      10.1254/jphs.12164FP

    • NAID

      10031156943

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pentazocine inhibits norepinephrine transporter function by reducing its surface expression in bovine adrenal medullary cells.2013

    • Author(s)
      Obara G, Toyohira Y, Inagaki H, Takahashi K, Horishita T, Kawasaki T, Ueno S, Tsutsui M, Sata T, Yanagihara N.
    • Journal Title

      J Pharmacol Sci.

      Volume: in press

    • NAID

      10031156943

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-Term Treatment with San’o-shashin-to, a Kampo Medicine, Markedly Ameliorates Cardiac Ischemia/Reperfusion Injury in Ovariectomized Rats via the Redox-Dependent Mechanism.2013

    • Author(s)
      Sakanashi M, Tsutsui M, et al.
    • Journal Title

      Circ J.

      Volume: in press

    • NAID

      10031173765

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stimulation of norepinephrine transporter function by fasudil, a Rho kinase inhibitor, in cultured bovine adrenal medullary cells2012

    • Author(s)
      Satoh N., ToyohiraY., Itoh H., Zhang H., Ueno S., Tsutsui M., Takahashi K., Yanagihara N.
    • Journal Title

      Naunyn-Schmiedeberg’s Archives of Pharmacology

      Volume: 385 Issue: 9 Pages: 921-931

    • DOI

      10.1007/s00210-012-0773-8

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Latest Evidence in Endothelium-Derived Hyperpolarizing Factor Research2012

    • Author(s)
      Tsutsui M, Ohya Y, Sugahara K
    • Journal Title

      Circulation Journal

      Volume: 76 Issue: 7 Pages: 1599-1600

    • DOI

      10.1253/circj.CJ-12-0654

    • NAID

      10030503134

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2013 Final Research Report
  • [Journal Article] Crucial vasculoprotective role of the whole nitric oxide synthase system in vascular lesion formation in mice : Involvement of bone marrow-derived cells2011

    • Author(s)
      Furuno Y., Morishita T., Toyohira Y., Yamada S., Ueno S., Morisada N., Sugita K., Noguchi K., Sakanashi M., Miyata H., Tanimoto A., Sasaguri Y., Shimokawa H., Otsuji Y., Yanagihara N., Tamura M., Tsuttsui M
    • Journal Title

      Nitric Oxide

      Volume: 25 Issue: 3 Pages: 350-359

    • DOI

      10.1016/j.niox.2011.06.007

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo2011

    • Author(s)
      Noguchi K, Hamadate N, Matsuzaki T, Sakanashi M, Nakasone J, Uchida T, Arakaki K, Kubota H, Ishiuchi S, Masuzaki H, Sugahara K, Ohya Y, Sakanashi M, Tsutsui M
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 301 Issue: 3 Pages: H721-H729

    • DOI

      10.1152/ajpheart.01089.2010

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle2011

    • Author(s)
      Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, Takahashi T, Inoue M, Itoh S, Takamoto I, Sasako T, Kumagai K, Kawai T, Hashimoto S, Kobayashi T, Sato M, Tokuyama K, Nishimura S, Tsunoda M, Ide T, Murakami K, Yamazaki T, EzakiO, Kawamura K, Masuda H, Moroi M, Sugi K, Oike Y, Shimokawa H, Yanagihara N, Tsutsui M, Terauchi Y, Tobe K, Nagai R, Kamata K, Inoue K, Kodama T, Ueki K, Kadowaki T
    • Journal Title

      Cell Metab

      Volume: 13(3) Issue: 3 Pages: 294-307

    • DOI

      10.1016/j.cmet.2011.01.018

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histamine deficiency decreases atherosclerosis and inflammatory response in apolipoprotein e knockout mice independently of serum cholesterol level2011

    • Author(s)
      Wang KY, Tanimoto A, Guo X, Yamada S, Shimajiri S, Murata Y, Ding Y, Tsutsui M, Kato S, Watanabe T, Ohtsu H, Hirano K, Kohno K, Sasaguri Y
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Issue: 4 Pages: 800-807

    • DOI

      10.1161/atvbaha.110.215228

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Eeduced spinal microglial activation and neuropathic pain after nerve injury in mice lscking all three nitric oxide synthases2011

    • Author(s)
      K.Kuboyama, M.Tsuda, M.Tsutsui, Y.Toyohara, H.Tozaki-Saitoh, H.Shimokawa, N.Yanagihara, K.Inoue
    • Journal Title

      Mol Pain

      Volume: 7 : 50 Pages: 50-50

    • DOI

      10.1186/1744-8069-7-50

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crucial vasculoprotective role of the whole nitric oxide synthase system in vascular lesion formation in mice: involvement of bone marrow-derived cells.2011

    • Author(s)
      Furuno Y, Morishita T, Toyohira Y, Yamada S, Ueno S, Morisada N, Sugita K, Noguchi K, Sakanashi M, Miyata H, Tanimoto A, Sasaguri Y, Shimokawa H, Otsuji Y, Yanagihara N, Tamura M, Tsutsui M.
    • Journal Title

      Nitric Oxide

      Volume: 25 Pages: 350-359

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle.2011

    • Author(s)
      Kubota T, Kubota N, ..., Tsutsui M, Terauchi Y, Tobe K, Nagai R, Kamata K, Inoue K, Kodama T, Ueki K, Kadowaki T.
    • Journal Title

      Cell Metabolism

      Volume: 13 Pages: 294-307

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Histamine deficiency decreases atherosclerosis and inflammatory response in apolipoprotein e knockout mice independently of serum cholesterol level.2011

    • Author(s)
      Wang KY, Tanimoto A, Guo X, Yamada S, Shimajiri S, Murata Y, Ding Y, Tsutsui M, Kato S, Watanabe T, Ohtsu H, Hirano K, Kohno K, Sasaguri Y.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Pages: 800-807

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo.2011

    • Author(s)
      Noguchi K, Hamadate N, Matsuzaki T, Sakanashi M, Nakasone J, Uchida T, Arakaki K, Kubota H, Ishiuchi S, Masuzaki H, Sugahara K, Ohya Y, Sakanashi M, Tsutsui M.
    • Journal Title

      Am J Physiol Heart Circ Physiol.

      Volume: 301

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduced spinal microglial activation and neuropathic pain after nerve injury in mice lacking all three nitric oxide synthases.2011

    • Author(s)
      Kuboyama K, Tsuda M, Tsutsui M, Toyohira Y, Tozaki-Saitoh H, Shimokawa H, Yanagihara N, Inoue K.
    • Journal Title

      Molecular Pain

      Volume: 7 Pages: 50-61

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Development of an Experimentally Useful Model of Spontaneous Myocardial Infarction : 2/3 Nephrectomized Triple Nitric Oxide Synthases-Deficient Mouse2014

    • Author(s)
      Uchida T, Furuno Y, Tanimoto H, Arakaki K, Kina M, Kubota H, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Ohya Y, Yanagihara N, Shimokawa H, Tamura M, Otsuji Y, Tsutsui M.
    • Organizer
      The 78th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Tokyo International Forum, Tokyo, Japan
    • Year and Date
      2014-03-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Significance of nitric oxide synthases in the cardiovascular system2013

    • Author(s)
      Tsutsui M
    • Organizer
      OIST - Ryukyu University Joint Seminar
    • Place of Presentation
      Okinawa Institute of Science and Technology, Okinawa, Japan
    • Year and Date
      2013-12-04
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel vasculoprotective role of nitric oxide synthases in bone marrow-derived vascular progenitor cells2013

    • Author(s)
      Tsutsui M, Furuno Y, Morishita T, Yanagihara N, Tamura M, Shimokawa H, Otsuji Y
    • Organizer
      American Heart Association, Scientific Sessions 2013
    • Place of Presentation
      Dallas Convention Center, Dallas, Texas, USA
    • Year and Date
      2013-11-18
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Development of an experimentally useful animal model of spontaneous myocardial infarction2013

    • Author(s)
      Uchida T, Furuno Y, Tanimoto A, Toyohira Y, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Ohya Y, Yanagihara N, Shimokawa H, Tamura M, Otsuji Y, Tsutsui M
    • Organizer
      The 77th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Year and Date
      2013-03-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Novel vasculoprotective role of nitric oxide synthase (NOS) in Mice : Involvement of Bone-Marrow-Derived Vascular Progenitor Cells2012

    • Author(s)
      Furuno Y, Tsutsui M, Morishita T, Shimokawa H, Otsuji Y, Yanagihara N, Kabashima N, Serino R, Kanegae K, Miyamoto T, Nakamata J, Ishimatsu N, Tamura M
    • Organizer
      The 49th European Renal Association-European Dialysis and Transplant Association Congress
    • Place of Presentation
      Palais des Congres, Paris, France
    • Year and Date
      2012-05-24
    • Related Report
      2013 Final Research Report
  • [Presentation] Novel vasculoprotective role of nitric oxide synthases in bone-marrow-derived vascular progenitor cells2012

    • Author(s)
      Tsutsui M, Furuno Y, Morishita T, Yanagihara N, Tamura M, Shimokawa H, Otsuji Y
    • Organizer
      The 76th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Fukuoka Kokusai Center, Fukuoka, Japan
    • Year and Date
      2012-03-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Accelerated Vascular Lesion Formation in Mice Lacking All Nitric Oxide Synthases : Contribution of Bone Marrow Cells2011

    • Author(s)
      Furuno Y, Morishita T, Yanagihara N, Shimokawa H, Otsuji Y, Tamura M, Tsutsui M
    • Organizer
      The 75th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Pacifico Yokohama, Yokohama, Japan
    • Year and Date
      2011-08-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Increasing dihydrobiopterin causese dysfunction of endothelial nitric oxide synthase in rats in vivo.2011

    • Author(s)
      Tsutsui M, Noguchi K, Matsuzaki T, Sakanashi M, Nakasone J, Uchida T, Arakaki K, Kubota H, Sugahara K, Ohya Y.
    • Organizer
      American Heart Association, Scientific Sessions 2011
    • Place of Presentation
      Orange County Convention Center, Orlando, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] NOと循環器病:遺伝子改変動物から得られた新知見2011

    • Author(s)
      筒井正人
    • Organizer
      日本臨床麻酔学会(招待講演)
    • Place of Presentation
      沖縄コンベンションセンター、沖縄
    • Related Report
      2011 Research-status Report
  • [Presentation] Development of an experimentally useful animal model of spontaneous myocardial infarction.

    • Author(s)
      Uchida T, Furuno Y, Tanimoto A, Toyohira Y, Sakanashi M, Matsuzaki T, Noguchi K, Nakasone J, Ohya Y, Yanagihara N, Shimokawa H, Tamura M, Otsuji Y, Tsutsui M.
    • Organizer
      The 77th Annual Scientific Meeting of the Japanese Circulation Society.
    • Place of Presentation
      Yokohama
    • Related Report
      2012 Research-status Report
  • [Presentation] 心血管系におけるNO合成酵素システムの意義

    • Author(s)
      筒井正人、下川宏明、尾辻豊、柳原延章
    • Organizer
      第86回日本薬理学会年会シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
    • Invited
  • [Remarks] ホームページ

    • URL

      http://w3.u-ryukyu.ac.jp/pharmaco/Pharmacology/youkoso_yao_lihe.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 琉球大学大学院医学研究科薬理学ホームページ

    • URL

      http://w3.u-ryukyu.ac.jp/pharmaco/Pharmacology/youkoso_yao_lihe.html

    • Related Report
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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