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Non-invasive Redox Imaging for the Pathophysiological Analysis of Hypertensive Renal Disease and Development of Antioxidative Therapy

Research Project

Project/Area Number 18590878
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTsukuba University of Technology (2007)
University of Tsukuba (2006)

Principal Investigator

HIRAYAMA Aki  Tsukuba University of Technology, Faculty of Health Sceinces, Professor (20323298)

Co-Investigator(Kenkyū-buntansha) YOH Keigyou  University of Tsukuba, Graduate School for Comprehensive Human Sciences, Associate Professor (90323302)
NAGASE Sohji  International University of Health and Welfare, School of Health Sciences, Professor (10189128)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsElectron Paramagnetic Resonance / Electron Paramagnetic Resonance Imaging / Hypertension / Ca Channel Antagonist / Angiotensin II Receptor Antagonist / Oxidative Stress
Research Abstract

The effect of calcium channel blocker azelnidipine on the redox status of a murine hypertension model was analyzed and imaged using in vivo low frequency electron paramagnetic resonance (EPR).
A murine two kidney-one clip (2K1C) hypertension model was made by a clipping of the right renal artery. The hypertensive mice were treated with low dose azelnidipine (1 mg/ kg/ day), high dose azelnidipine (3 mg /kg /day) or without azelnidipine (HT). An EPR system equipped with a loop-gap resonator and an imaging system was employed. Redox status was evaluated as organ reducing activity measured by means of the decay rate (half-lives) of the spin probe 3-carbamoyl-2, 2, 5, 5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL).
Four weeks after clipping the mice showed hypertension. After the additional two weeks of Azl treatments the Carbamoyl-PROXYL half-lives of the Low and High Azl groups measured in the upper abdominal area were significantly shorter than those of the HT group suggesting improvements in the reducing activity. The blood pressures of the three groups showed no significant differences at this time and there was no correlation between the renal reducing activity and either blood pressure or serum creatinine values. EPR imaging studies revealed that the improvement in abdominal reducing activity was mainly recognized in the kidney but not in the liver.
These results indicate that azelnidipine ameliorates the renal redox status through an improvement in reducing activity independent of blood pressure control.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (32 results)

All 2008 2007 2006 Other

All Journal Article (19 results) (of which Peer Reviewed: 7 results) Presentation (12 results) Book (1 results)

  • [Journal Article] In vivo imaging of renal redox status during azelnidpine treatments2008

    • Author(s)
      Hirayama A.
    • Journal Title

      Hypertension Research (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Nitric oxide protection against adriamycin-induced tubulointerstitial injury.2008

    • Author(s)
      Oteki T.
    • Journal Title

      Free Radical Research 42(2)

      Pages: 154-161

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] In vivo imaging of renal redox status during azelnidpine treatments2008

    • Author(s)
      Hirayama A.
    • Journal Title

      Hypertension Research (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of CV159 - Ca^<2+> / Calmodulin blockade - on redox status hepatic ischemia reperfusion injury in mice evaluated by newly developed in vivo EPR imaging technique2008

    • Author(s)
      Kobayashi H.
    • Journal Title

      Journal of Surgical Research 147-1

      Pages: 41-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] In vivo detection of intrinsic reactive oxygen species using acyl-protected hydroxylamine in puromycin nephrosis.2007

    • Author(s)
      Ueda A.
    • Journal Title

      Free Radical Research 41(7)

      Pages: 823-828

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effect of CV159-Ca^<2+>/Calmodulin blockade-on redox status hepatic ischemia reperfusion injury in mice evaluated by newly developed in vivo EPR imaging technique.2007

    • Author(s)
      Kobayashi H.
    • Journal Title

      Journal of Surgical Research

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Elimination of lipid peroxide during hemodialysis.2007

    • Author(s)
      Obara M
    • Journal Title

      Nephron Clinical Practice 106

      Pages: 162-168

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Oral administration of proanthocyanidin elevates radical scavenging activity in plasma and muscle tissue in rat.2007

    • Author(s)
      Masuda K
    • Journal Title

      Applied Physiology, Nutrition and Metabolism 32

      Pages: 1097-1104

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] In vivo detection of intrinsic reactive oxygen species using acyl-protected hydroxylamine in puromycin nephrosis2007

    • Author(s)
      Ueda A.
    • Journal Title

      Free Radical Research 41-7

      Pages: 823-828

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Nitric oxide protection against adriamycin-induced tubulointerstitial injury2007

    • Author(s)
      Oteki T.
    • Journal Title

      Free Radical Research 42-2

      Pages: 154-161

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Elimination of lipid peroxide during hemodialysis2007

    • Author(s)
      Obara M.
    • Journal Title

      Nephron Clinical Practice 106-2

      Pages: 162-168

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Oral administration of proanthocyanidin elevates radical scavenging activity in plasma and muscle tissue in rat2007

    • Author(s)
      Masuda K.
    • Journal Title

      Applied Physiology, Nutrition and Metabolism 32

      Pages: 1097-1104

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of CV159-Ca^<2+>/Calmodulin blockade-on redox status hepatic ischemia reperfusion injury in mice evaluated by newly developed in vivo EPR imaging technique.2007

    • Author(s)
      Kobayashi H.
    • Journal Title

      Journal of Surgical Research (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electron paramagnetic resonance imaging of oxidative stress in renal disease.2006

    • Author(s)
      Hirayama A
    • Journal Title

      Nephron Clinical Practice 103

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of Spontaneous Exercise on Antioxidant Capacity in Rat Muscles Determined by Electron Spin Resonance.2006

    • Author(s)
      Tanabe K
    • Journal Title

      Acta Physiologica 186

      Pages: 119-125

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Relationships between Age, Daily Physical Activity, Antioxidant Capacity and Oxidative Stress among Middle-Aged and Elderly People.2006

    • Author(s)
      Tanabe K
    • Journal Title

      International Journal of Sport and Health Science 4(special issue 2)

      Pages: 515-527

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Renal redox imaging and in vivo analysis during antihypertensive treatments.2006

    • Author(s)
      Hirayama A
    • Journal Title

      Nephrology Dialysis Transplantation 21・Suppl.4

      Pages: 41-42

    • Related Report
      2006 Annual Research Report
  • [Journal Article] In vivo detection of intrinsic reactive oxygen species using acyl-protected hydroxylamine in puromycin nephrosis.

    • Author(s)
      Ueda A
    • Journal Title

      Free Radical Research (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Elimination of lipid peroxide during hemodialysis.

    • Author(s)
      Obara M
    • Journal Title

      Nephron Clinical Practice (In press)

    • Related Report
      2006 Annual Research Report
  • [Presentation] In vivo EPR analysis and imaging of antihypertensive drugs on renal reducing activity.2007

    • Author(s)
      Hirayama A.
    • Organizer
      EPR 2007: A Joint Conference of 12th In Vivo EPR Spectroscopy and Imaging 9th International EPR Spin Trapping/Spin Labeling
    • Place of Presentation
      シカゴ(米国)
    • Year and Date
      2007-04-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] In vivo EPR analysis and imaging of antihypertensive drugs on renal reducing activity2007

    • Author(s)
      Hirayama A.
    • Organizer
      EPR 2007: A Joint Conference of 12th In Vivo EPR Spectroscopy and Imaging 9th International EPR Spin Trapping/ Spin Labeling
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2007-04-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Imbalance of Mitochondrial Superoxide and Intracellular Nitric Oxide in the Hyperproteinuric Phase of Puromycin Nephrosis.2007

    • Author(s)
      Hirayama A.
    • Organizer
      40th annual meeting of the American Society of Nephrology
    • Place of Presentation
      サンフランシスコ(米国)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Triglyceride Rich Lipoproteins Contribute to the Decline in Renal Function in Experimental Chronic Renal Failure (CRF) Rats and the Oral Adsorbent AST-120 (Kremedine) Alters This Process.2007

    • Author(s)
      Owada S.
    • Organizer
      40th annual meeting of the American Society of Nephrology
    • Place of Presentation
      サンフランシスコ(米国)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 肝虚血再灌流障害におけるElectron paramagnetic resonance imaging (EPRI)による臓器還元能評価2007

    • Author(s)
      小林博通
    • Organizer
      第107回日本外科学会定期学術集会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 血液透析の抗酸化的側面 ワークショップ「透析患者の酸化ストレスUp to date」2007

    • Author(s)
      平山 暁
    • Organizer
      第52回日本透析医学会総会・学術集会
    • Place of Presentation
      大阪
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Imbalance of Mitochondrial Superoxide and Intracellular Nitric Oxide in the Hyperproteinuric Phase of Puromycin Nephrosis2007

    • Author(s)
      Hirayama A.
    • Organizer
      40th annual meeting of the American Society of Nephrology
    • Place of Presentation
      San Francisco, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Triglyceride Rich Lipoproteins Contribute to the Dedine in Renal Function in Experimental Chronic Renal Failure (CRF) Rats and the Oral Adsorbent AST-120 (Kremedine) Alters This Process2007

    • Author(s)
      Owada S.
    • Organizer
      40th annual meeting of the American Society of Nephrology
    • Place of Presentation
      San Francisco, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Kan Kyoketsu-Saikanryu Shougai ni okeru Electron paramagnetic resonance imaging (EPRI) ni yoru Zouki Kangennnou Hyouka2007

    • Author(s)
      Kobayashi H.
    • Organizer
      107th Annual Meeting of Japanese Society of Surgery
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Ketsueki Touseki no Kousanka-teki Sokumen (Antioxidataive Effects of Hemodialysis), Workshop: Oxidative Stress in Dialysis Patients, UP to DATE2007

    • Author(s)
      Hirayama A.
    • Organizer
      52nd Annual Meeting of Japanese Society for Dialysis Therapy
    • Place of Presentation
      Osaka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Triglyceride Rich Lipoproteins Contribute to the Decline in Renal Function in Experimental Chronic Renal Failure(CRF)Rats and the Oral Adsorbent AST-120(Kremedine)Alters This Process.2007

    • Author(s)
      Owada S.
    • Organizer
      40th annual meeting of the American Society of Nephrology
    • Place of Presentation
      サンフランシスコ(米国)
    • Related Report
      2007 Annual Research Report
  • [Presentation] 肝虚血再灌流障害におけるElectron paramagnetic resonance imaging(EPRI)による臓器還元能評価2007

    • Author(s)
      小林博通
    • Organizer
      第107回日本外科学会定期学術集会
    • Place of Presentation
      大阪
    • Related Report
      2007 Annual Research Report
  • [Book] Nitric Oxide from Inducible Nitric-Oxide Synthase Does not Exacerbate Adriamycin-Induced Tubulointerstitial Injury. in; The Proceedings of the XIII Congress of the Society for Free Radical Research International.2006

    • Author(s)
      Oteki T
    • Total Pages
      352
    • Publisher
      Medimond SRL
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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