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Role of nitric oxide in reactive oxygen species-dependent intracellular signal transduction in cardiovascular tissue

Research Project

Project/Area Number 19590250
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionKagawa University

Principal Investigator

KIMURA Shoji  Kagawa University, 医学部, 准教授 (30253264)

Co-Investigator(Kenkyū-buntansha) NAGAI Yukiko  香川大学, 医学部, 教務職員 (30335864)
西山 成  香川大学, 医学部, 教授 (10325334)
大森 浩二  香川大学, 医学部, 准教授 (00263913)
張 國興  香川大学, 医学部, 助教授 (90444728)
宮武 明  香川大学, 総合生命科学実験センター, 准教授 (80211598)
Co-Investigator(Renkei-kenkyūsha) NISHIYAMA Akira  香川大学, 医学部, 教授 (10325334)
OHMORI Koji  香川大学, 医学部, 准教授 (00263913)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords高血圧 / 酸化ストレス / 一酸化窒素合成酵素 / アンジオテンシン / 活性酸素 / MAPキナーゼ / ミトコンドリア / 血管平滑筋
Research Abstract

神経型一酸化窒素合成酵素(NOS)由来NOは、平常時にはラジカルスカベンジャーとして心血管MAPキナーゼ活性化には抑制的に働いていている。一方でアンジオテンシンII暴露時には、NADPHオキシダーゼが関わる活性酸素産生系を強力に誘導されることから、神経型NOS由来NOとの反応によりperoxynitriteの産生増強が起り、これが逆に心血管MAPキナーゼの酸化ストレス依存性の活性化を引き起こしていた。これら成果から、心血管系酸化ストレスに及ぼす神経型NOSの相反する2面性が判明した。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (56 results)

All 2009 2008 2007

All Journal Article (20 results) (of which Peer Reviewed: 19 results) Presentation (34 results) Book (2 results)

  • [Journal Article] The opposite roles of nNOS in cardiac ischemia-reperfusion-induced injury and in ischemia preconditioning-induced cardioprotection in mice.2009

    • Author(s)
      Lu XM, Zhang GX, Yu YQ, Kimura S, Nishiyama A, Matsuyoshi H, Shimizu J, Takaki M.
    • Journal Title

      J Physiol Sci.

    • NAID

      10025218967

    • Related Report
      2008 Final Research Report
  • [Journal Article] Role of neuronal NO synthase in regulating vascular superoxide levels and mitogen-activated protein kinase phos2009

    • Author(s)
      Zhang GX, Kimura S, Murao K, Shimizu J, Matsuyoshi H, Takaki M.
    • Journal Title

      Cardiovasc Res 81

      Pages: 389-399

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of neuronal NO synthase in regulating vascular superoxide levels and mitogen-activated protein kinase phosphorylatlon.2009

    • Author(s)
      Zhang, et al.
    • Journal Title

      Cardiovasc Res. 81

      Pages: 389-399

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The opposite roles of nNOS in cardiac ischemia-reperfusion-induced injury and in ischemia preconditioning-induced cardioprotection in mice.2009

    • Author(s)
      Lu, et al.
    • Journal Title

      J Physiol Sci. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulating effect of the PI3-kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells2008

    • Author(s)
      Fujiwara M, Izuishi K, Sano T, HossainMA, Kimura S, Masaki T, Suzuki Y.
    • Journal Title

      J Exp Clin Cancer Res 27 : 76

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone induces myofibroblastic transdifferentiation and collagen gene expression through the Rho-kinase dependent signaling pathway in rat mesangial cells2008

    • Author(s)
      Diah S, Zhang GX, Nagai Y, Zhang W, Gang L, Kimura S, Hamid MRWA, Tamiya T, Nishiyama A, Hitomi H.
    • Journal Title

      Exp Cell Res 314

      Pages: 3654-3662

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of Rho-kinase in aldosterone-induced vascular remodeling2008

    • Author(s)
      Miyata K, Sun GP, Guo P, Hitomi H, Kimura S, Kiyomoto H, Hosomi N, Kohno M and Nishiyama A.
    • Journal Title

      Hypertens Res 31

      Pages: 1407-1413

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modulating effect of the PI3-kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells.2008

    • Author(s)
      Fujiwara, et al.
    • Journal Title

      J Exp Clin Cancer Res. 27

      Pages: 76-76

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible involvement of Rho-kinase in aldosterone-induced vascular smooth muscle cell remodeling.2008

    • Author(s)
      Miyata, et al.
    • Journal Title

      Hypertens Res. 31

      Pages: 1407-1413

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aldosterone induces myofibroblastic transdifferentiation and collagen gene expression through the Rho-kinase dependent signaling pathway in rat mesangial cells.2008

    • Author(s)
      Diah, et al.
    • Journal Title

      Exp Cell Res. 314

      Pages: 3654-3662

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases2007

    • Author(s)
      Zhang GX, Nagai Y, Nakagawa T, Miyanaka H, Fujisawa Y, Nishiyama A, Izuishi K, Ohmori K, Kimura S.
    • Journal Title

      Am J Physiol Heart Circ Physiol 293

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Preventive effect of D-psicose, one of rare ketohexoses, on di-(2-ethylhexyl) phthalate (DEHP)-induced testicular injury in rat2007

    • Author(s)
      Suna S, Yamaguchi F, Kimura S, Tokuda M, Jitsunari F.
    • Journal Title

      Toxicol Lett 173

      Pages: 107-117

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mi2007

    • Author(s)
      Zhang GX, Ohmori K, Nagai Y, Fujisawa Y, Nishiyama A, Abe Y, Kimura S
    • Journal Title

      J Mol Cell Cardiol 42

      Pages: 804-811

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of adrenomedullin 2 on regional hemodynamics in conscious rats2007

    • Author(s)
      Fujisawa Y, Nagai Y, Miyatake A, Miura K, Nishiyama A, Kimura S, Abe Y.
    • Journal Title

      Eur J Pharmacol 558

      Pages: 128-132

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of mitochondria in angiotensn II-induced reactive oxygen species and mitogen-activated protein kinase activation2007

    • Author(s)
      Zhang GX, Lu XM, Kimura S, Nishiyama A.
    • Journal Title

      Cardiovasc Res 76

      Pages: 204-212

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of endogenous nitric oxide in Angiotensin II-induced activation of vascular mitogen-activated protein kinases2007

    • Author(s)
      Zhang, et. al.
    • Journal Title

      Am J Physiol Heart Circ Physiol 293

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of AT1 receptor in isoproterenol-induced cardiac hypertrophy and oxidative stress in mice2007

    • Author(s)
      Zhang, et. al.
    • Journal Title

      J Mol Cell Cardiol 42

      Pages: 804-811

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of mitochondria angiotensn II-induced reactive oxygen species and mitogen-activated protein kinase activation2007

    • Author(s)
      Zhang, et. al.
    • Journal Title

      Cardiovasc Res 76

      Pages: 204-212

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preventive effect of D-psicose,one of rare ketohexoses,on di-(2-ethyulhexyl)phthalate(DEHP)-induced testicular injury in rat2007

    • Author(s)
      Suna S, et. al.
    • Journal Title

      Toxicol Lett 173

      Pages: 107-117

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of adrenomedullin 2 on regional hemodynamics in conscious rats2007

    • Author(s)
      Fujisawa, et. al.
    • Journal Title

      Eur J Pharmacol 558

      Pages: 128-132

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 高食塩負荷ラットにおける腎孟内圧の循環血行動態への影響2009

    • Author(s)
      藤澤良秀 等
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横 浜
    • Year and Date
      2009-03-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] アルドステロンは腎臓における老化を加速する2009

    • Author(s)
      Yu-yan Fan等
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Final Research Report
  • [Presentation] アルドステロンは腎臓における老化を加速する2009

    • Author(s)
      Yu-yan Fan 等
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横 浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] メクボリックシンドロームモデルラットにおける腎内レニン・アンジオテンシン系および酸化ストレスの増大をシルニジピンは抑制する2009

    • Author(s)
      Yu-yan Fan等
    • Organizer
      第82回日本薬理学会年次
    • Place of Presentation
      横 浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] アンジオテンシンI Iによる血管平滑筋におけるインスリンシグナル伝達に対する影響2009

    • Author(s)
      人見浩史 等
    • Organizer
      第82回日本薬理学会年次
    • Place of Presentation
      横 浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] 血管平滑筋における進展刺激とアンジオテンシンIIの増殖効果伝に対する影響2009

    • Author(s)
      劉鋼 等
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横 浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Effects of Angiotensin II receptor blocker on tissue expression balance between Angiotensin II receptor and its inhibitory binding molecls.2008

    • Author(s)
      Kazi Rafiq, et al.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札 幌
    • Year and Date
      2008-10-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Effects of cilnidipine on intrarenal rennin-angiotensin system, oxidative stress and renal injury- in SHR/ND rats.2008

    • Author(s)
      Yu-yan Fan, et al.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札 幌
    • Year and Date
      2008-10-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Effects of azelnidipine on oxidative stress and renal injury in aldosterone-induced hypertensive rats.2008

    • Author(s)
      Yu-yan Fan, et al.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札 幌
    • Year and Date
      2008-10-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] Mechanical stretch potentiates angiotensin II-induced prolifer ation in spontaneously hypertensive rat vascular smooth muscle cells.2008

    • Author(s)
      Gang Liu, et al.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札 幌
    • Year and Date
      2008-10-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 培養ラット平滑筋細胞では機械的伸展刺激によって11β-HSD2発現が減少する2008

    • Author(s)
      永井由紀子他
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-10-09
    • Related Report
      2008 Final Research Report
  • [Presentation] Mechanical stretch potentiates angiotensin II-induced proliferation in spontaneously hypertensive rat vascular smooth muscle cells2008

    • Author(s)
      Gang Liu et.al.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-10-09
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of Angiotensin II receptor blocker on tissue expression balance between Angiotensin II receptor and its inhibitory binding molecls2008

    • Author(s)
      Kazi Rafiq et.al.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-10-09
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of cilnidipine on intrarenal rennin-angiotensin system, oxidative stress and renal injury in SHR/ND rats2008

    • Author(s)
      Yu-yan Fan et.al.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-10-09
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of azelnidipine on oxidative stress and renal injury in aldosterone-induced hypertensive rats2008

    • Author(s)
      Yu-yan Fan et.al.
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-10-09
    • Related Report
      2008 Final Research Report
  • [Presentation] 培養ラット平滑筋細胞では機械的伸展刺激によって11β-HSD2発現が減少する2008

    • Author(s)
      永井 由紀子, 他
    • Organizer
      第31回日本高血圧学会総会
    • Place of Presentation
      札 幌
    • Year and Date
      2008-10-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] 培養ラット平滑筋細胞fでは機械的進展刺激により11β-HDS2発現が減少する2008

    • Author(s)
      永井由紀子, 他
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-17
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] マウス虚血・プレコンディショニングにおけるnNOSの役割2008

    • Author(s)
      ルシャオメイ, 他
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-17
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] ラットメザンギウム細胞においてアルドステロンはRhoキナーゼ系を活性化してコラーゲンI発現と形質転換を生じる2008

    • Author(s)
      ディアスワニー, 他
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-17
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] アルドステロン依存性高血圧ラットにおけるアゼルニピンの酸化ストレスと腎障害に対する効果2008

    • Author(s)
      ハンユウヤン, 他
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-17
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] 腎盂内圧上昇の循環血行動態への影響2008

    • Author(s)
      藤澤良秀, 他
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-17
    • Related Report
      2008 Final Research Report
  • [Presentation] 腎孟内圧上昇の循環血行動態への影響2008

    • Author(s)
      藤澤 良秀, 他
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases2007

    • Author(s)
      Zhang GX et.al.
    • Organizer
      第9回日中高血圧シンポジウム
    • Place of Presentation
      Beijin, China
    • Year and Date
      2007-11-11
    • Related Report
      2008 Final Research Report
  • [Presentation] 2型糖尿病ラットにおける腎症顕性期からのオルメサルタンの腎保護作用2007

    • Author(s)
      伊原玄英, 他
    • Organizer
      第30回日本高血圧学会総会
    • Place of Presentation
      宜野湾
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] ハムスター尿管閉塞モデルにおけるキマーゼを介したアンジオテンシンII産生と腎間質線維化作用2007

    • Author(s)
      氾愈燕, 他
    • Organizer
      第30回日本高血圧学会総会
    • Place of Presentation
      宜野湾
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] 食塩負荷はアンジオテンシンIIによる血管平滑筋細胞の増殖作用を増強する2007

    • Author(s)
      人見浩史, 他
    • Organizer
      第30回日本高血圧学会総会
    • Place of Presentation
      宜野湾
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Involvement of endogenous nitric oxide in Angiotensin II-induced activation of vascular mitogen-activated protein kinases2007

    • Author(s)
      Zhang GX et.al.
    • Organizer
      第30回日本高血圧学会総会
    • Place of Presentation
      宜野湾
    • Year and Date
      2007-10-25
    • Related Report
      2008 Final Research Report
  • [Presentation] The role of chymase in angiotensin II formation and progression of fibrosis in obstructed kidneys2007

    • Author(s)
      Fan Y-Y et.al.
    • Organizer
      kidneys. 9^<th> International Symposium
    • Place of Presentation
      Tucson, USA
    • Year and Date
      2007-09-04
    • Related Report
      2008 Final Research Report
  • [Presentation] フルクトース負荷ラットで生じるインスリン抵抗性におけるプロレニンの関与2007

    • Author(s)
      永井由紀子, 他
    • Organizer
      第30回日本高血圧学会総会
    • Place of Presentation
      宜野湾
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases2007

    • Author(s)
      Zhang, et. al.
    • Organizer
      9^<th> Intemational Symposium on Hypertension and Related Diseases
    • Place of Presentation
      Beijing,Caina
    • Related Report
      2007 Annual Research Report
  • [Presentation] The role of chymase in angiotensin II formation and progression of fibrosis in obstructed kidneys2007

    • Author(s)
      Fan Y-Y, et. al.
    • Organizer
      61st Annual High Blood Pressure Research Conference
    • Place of Presentation
      Tucson,USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Mechanical stretch-induced reduction in 11beta-hydroxysteroid dehydrogen ase2expression in rat vascular smooth muscle cells2007

    • Author(s)
      Yukiko Nagai, et. al.
    • Organizer
      61st Annual High Blood Pressure Research Conference
    • Place of Presentation
      Tucson,USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Involvement of endogenous nitric oxide in Angiotensin II-induced activation of vascular mitogenactivated protein kinases2007

    • Author(s)
      Zhang, et. al.
    • Organizer
      第30回日本高血圧学会総会
    • Place of Presentation
      宜野湾
    • Related Report
      2007 Annual Research Report
  • [Presentation] Effects of 10-N-nonyl acridine orange(NAO)on ischemic/reperfusion injury in rat heart2007

    • Author(s)
      張 国興, 他
    • Organizer
      第7回日本NO学会学術集会
    • Place of Presentation
      滋賀
    • Related Report
      2007 Annual Research Report
  • [Book] D-allose suppresses development of hypertension in salt-loaded spontaneously hypertensive rats(RARE SUGARS II, Edited by Asada Y, Kawanami Y, Tajima S)2008

    • Author(s)
      Zhang GX, Nagai Y, Fujisawa Y, Nishiyama A, Kimura S.
    • Publisher
      Art-Printing Co. Ltd.
    • Related Report
      2008 Final Research Report
  • [Book] D-psicose, a rare sugar, prevents Di-(2-ethylhexyl)phthalate (DEHP)-induced testicular injury by suppressing the generation of reactive oxygen species in rat testis(RARE SUGARS II, Edited by Asada Y, Kawanami Y, Tajima S)2008

    • Author(s)
      Suna S, Jistunari F, Tokuda M, Yamaguchi F, Kimura S
    • Publisher
      Art-Printing Co. Ltd.
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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