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New Treatment for Nephropathy with the Normalization of Tubulo-Glomerular Feedback Mechanisms

Research Project

Project/Area Number 16390158
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

ABE Youichi  Kagawa University, Faculty of Medicine, Professor, 医学部, 教授 (10047227)

Co-Investigator(Kenkyū-buntansha) NISHIYAMA Akira  Kagawa University, Faculty of Medicine, Assistant, 医学部, 助手 (10325334)
KIMURA Shoji  Kagawa University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30253264)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥9,900,000 (Direct Cost: ¥9,900,000)
KeywordsTubulo-glomerular feedback / Afferent arteriole / Nephropathy / Hypertension / Dahl salt-sensitive rats / ATP / P2 receptor / Suramin / P2受容体
Research Abstract

It is speculated that an abnormal tubulo-glomerular feedback (TGF) activity may induce the nephropathy via renal hemodynamic changes. However, there are no useful technique to evaluate the TGF activity. In addition, the transmitters from macula densa cells to afferent arterioles have not been determined yet. We have fortunately solved the first problem by introducing the in vivo dynamic method to evaluate TGF activity. So, the purposes of this project are to determine the transmitter in TGF mechanisms and to develop the new strategy for the treatment of nephropathy by the normalization of TGF activity.
1.Determination of mediators in TGF mechanisms : The renal interstitial concentration of adenosine, ATP and NO metabolites. We observed the positive correlation between TGF-mediated changes in renal vascular resistance and renal interstitial concentration of ATP. Thus, we could pick up ATP for the candidate of TGF mediator.
2.TGF activity in Dahl salt -sensitive (DS) rats : DS rars were ma … More intained on low(L:0.3% NaCl) or high salt(H:8% NaCl) diets for 4 weeks. Using in vivo dynamic method described above, superficial afferent arteriolar diameter (AAD) was measured before and during enhanced TGF activity induced by acetazolamide(ACZ). Compared to DS・L rats, DS・H rats showed smaller basal AAD. ACZ significantly decreased, AAD in DS・L rats, but did not change AAD in DS・H rats. Furosemide increased AADs in both rats. These findings indicate an enhancement of TGF activity in DS・H rats.
3.Effect of P2 receptor antagonist, suramin, on TGF activity in DS・H rats : Treatment of suramin significantly increased basal AAD, but AAD did not change during administration of ACD and furosemide, indicating suramin normalized the enhanced TGF activity in DS・H rats.
4.Effects of suramin on blood pressure and urinary excretion of protein : Suramin markedly attenuated the development of hypertension and decreased the urinary protein excretion in DS・H rats.
The result indicates that the development of nephropathy and hypertension is associated with an enhancement of TGF activity in DS・H rats. P2 receptor antagonist should be a good agent for the treatment of nephropathy. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (24 results)

All 2006 2005 2004

All Journal Article (24 results)

  • [Journal Article] Effects of calcium channel blockade on angiotensin II-induced peritubular ischemia in rats.2006

    • Author(s)
      Kondo Naoki
    • Journal Title

      J.Pharmacol.Exp.Ther. 316

      Pages: 1047-1052

    • Related Report
      2005 Annual Research Report
  • [Journal Article] D-allose, an all-cis aldo-hexose, suppresses development of salt induced hypertension in Dahl rats.2005

    • Author(s)
      Kimura Shoji
    • Journal Title

      J. Hypertension 23

      Pages: 1887-1894

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Temporaty angiotensin blockade at the prediabetic stage attbuates the development of type 2 diabetic nephropathy.2005

    • Author(s)
      Nagai Yukiko
    • Journal Title

      J. Am. Soc. Nephrol. 16

      Pages: 703-711

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability.2005

    • Author(s)
      Nishiyama Akara
    • Journal Title

      Hypertension 45

      Pages: 710-716

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] D-allose, an all-cis aldo-hexose, suppresses development of salt induced hypertension in Dahl rats.2005

    • Author(s)
      Kimura Shoji
    • Journal Title

      J.Hypertension 23

      Pages: 1887-1894

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Temporary angiotensin blockade at the prediabetic stage attnuates the development of type 2 diabetic nephropathy2005

    • Author(s)
      Nagai Yukiko
    • Journal Title

      J.Am.Soc.Nephrol. 16

      Pages: 703-711

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferat ion and deformability.2005

    • Author(s)
      Nishiyama Akira
    • Journal Title

      Hypertension 45

      Pages: 710-716

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] D-allose, an all-cis aldo-hexose, suppresses development of salt-induced hypertension in Dahl rats.2005

    • Author(s)
      Kimura Shoji
    • Journal Title

      J.Hypertension 23

      Pages: 1887-1894

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Temporary angiotensin II blockade at the prediabetic stage attnuates the development of renal injury in type 2 diabetic rats.2005

    • Author(s)
      Nagai Yukiko
    • Journal Title

      J.Am.Soc.Nephrol. 16

      Pages: 703-711

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Involvement of aldosterone and mineralocorticoid receptors in rat mesangial cell proliferation and deformability.2005

    • Author(s)
      Nishiyama Akira
    • Journal Title

      Hypertension 45

      Pages: 710-716

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aldosterone stimulates collagen gene expression and synthesis via activation of extracellular signal-regulated kinases in renal fibroblasts.2005

    • Author(s)
      Nagai Yukiko
    • Journal Title

      Hypertension 46

      Pages: 1039-1045

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aldosterone stimulates reactive oxygen species production through the activation of NADPH oxidase in rat mesangial cells.2005

    • Author(s)
      Miyata Kayoko
    • Journal Title

      J.Am.Soc.Nephrol. 16

      Pages: 2906-2912

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mitochondria-derived reactive oxygen species and vascular MAP kinase : comparison of angiotensin II and diazoxide.2005

    • Author(s)
      Kimura Shoji
    • Journal Title

      Hypertension 45

      Pages: 438-444

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Temporary Angiotensin II Blockade at the Prediabetic Stage Attenuates the Development of Renal Injury in Type 2 Diabetic Rats.2005

    • Author(s)
      Nagai Yukiko
    • Journal Title

      J.Am.Soc.Nephrol. 16

      Pages: 703-711

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The SOD mimetic tempol ameliorates glomerular injury and reduces mitogen-activated protein kinase activity in Dahl salt-sensitive rats.2004

    • Author(s)
      Nishiyama Akira
    • Journal Title

      J. Am. Soc. Nephrol. 15

      Pages: 306-315

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of AT1 receptor blockade on renal injury and mitogen-activated protein kinase activity in Dah1 salt-sensitive rats.2004

    • Author(s)
      Nishiyama Akira
    • Journal Title

      Kidney Int. 65

      Pages: 972-981

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of interstitial ATP and adenosine in the regulation of renal hemodynamics and microvascular function.2004

    • Author(s)
      Nihsiyama Akira
    • Journal Title

      Hypertens. Res. 27

      Pages: 791-804

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The SOD mimetic tempol ameliorates glomerular injury and reduces mitogen-activated protein kinase activity in Dahl salt-sensitive rats.2004

    • Author(s)
      Nishiyama Akira
    • Journal Title

      J.Am.Soc.Nephrol. 15

      Pages: 306-315

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of AT1 receptor blockade on renal injury and mitogen-activated protein kinase activity in Dahl salt-sensitive rats.2004

    • Author(s)
      Nishiyama Akira
    • Journal Title

      Kidney Int. 65

      Pages: 972-981

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of interstitial ATP and adenosine in the regulation of renal hemodynamics and microvascular function.2004

    • Author(s)
      Nishiyama Akira
    • Journal Title

      Hypertens. Res. 27

      Pages: 791-804

    • NAID

      10014387419

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Time-dependent transition of tempol-sensitive reduction of blood pressure in angiotensin II-induced hypertension.2004

    • Author(s)
      Kimura Shoji
    • Journal Title

      J.Hypertens. 22

      Pages: 2161-2168

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Renal effects of a new member of adrenomedullin family, adrenomedullin2, in rats.2004

    • Author(s)
      Fujisawa Yoshihide
    • Journal Title

      Eur.J.Pharmacol. 497

      Pages: 75-80

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats.2004

    • Author(s)
      Nishiyama Akira
    • Journal Title

      Kidney Int. 65

      Pages: 972-981

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats.2004

    • Author(s)
      Nishiyama Akira
    • Journal Title

      Hypertension 43

      Pages: 841-848

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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