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Role of Angiotensin (1-7) in therapeutic application of inhibition of rennin-angiotensin system in man

Research Project

Project/Area Number 13670734
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of the Ryukyus (2002-2003)
Yokohama City University (2001)

Principal Investigator

UEDA Shinichiro  University of the Ryukyus, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (80285105)

Co-Investigator(Kenkyū-buntansha) TAKISHITA Syuichi  University of the Ryukyus, Faculty of Medicine, Professor, 医学部, 教授 (90108712)
SHIMABUKURO Michio  University of the Ryukyus, University Hospital, Assistants Professor, 医学部附属病院, 講師 (60271144)
YASUNARI Kenichi  Osaka City University Graduate School of medicine, Graduate School of Medicine, Assistants Professor, 医学部, 講師 (90231646)
梅村 敏  横浜市立大学, 医学部, 教授 (00128589)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsangiotensin(1-7) / Angiotensin II / bradykinin / oxidative stress / AGE inhibitor / Nitric Oxide / RCT of diuretics / 心不全 / ACE阻害薬 / アンジオテンシン変換酵素 / 前腕血流量 / プレシスモグラフ
Research Abstract

1.Interaction of Angiotensin(1-7) with bradykin and other vasoactive peptides in human resistant vessels in vivo
Angiotensin(1-7) significantly potentiated vasodilating effect of bradykinin in dose-dependent manner possibly through NO system. This result is completely consistent with previous results from studies in isolated vessels.
2.Validation of NO clamp technique in human NO research in vivo
We evaluated validity and feasibility of NO damp technique for NO research using L-NMMA for NOS inhibition.
3.Anticoxidant effect of Angiotensin(1-7) in vitro and in vivo
We showed Angiotensin II attenuated vasodilating effect of a NO donor possibly through increased production of superoxide in human resisitant vessels. This effect was antagonized by co-infusion of Angiotensin(1-7) in dose dedpendent manner. Angiotensin(1-7) was also found to inhibit increased oxidative stress by Angiotensin II in cultured human THP-1 cells.
4.Increased Angiotensin(1-7) levels in patients with hypertension receiving ACE inhibitors. The single dose of captopril significantly elevated plasma levels of angiotensin-(1-7) in hypertensives and normal volunteers. There was highly significant correlation between changes in plasma levels of angiotensin-(1-7) and blood pressure. Plasma angiotensin-(1-7) levels in hypertensive patients chronically receiving ACE inhibitors were significantly higher than those without AGE inhibitors while there was no significant difference in plasma Angiotensin II levels. Either acute or chronic treatment with ACE inhibitors was associated with increased plasma levels of angiotennsin-(1-7), which may contribute to effects of ACF inhibitions.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Shimabukuro M, et al.: "Hypoadiponectinemia is closely linked to endothelial dysfunction in man."J Clin Endocrinol Metab.. 88. 3236-3240 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wada A, et al.: "Angiotensin II attenuates the vasodilating effect of a nitric oxide donor, glyceryl trinitrate. Roles of superoxide and angiotensin II type1 receptors."Clin Pharmacol Ther. 6. 440-447 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueda S, et al.: "Angiotensin (1-7) potentiates bradykinin-induced vasodilation in man."J Hypertens. 19. 2001-2009 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasunari K et al.: "Effects of carvediol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension."Am J Med.. 116. 460-465 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueda S, et al.: "Validity and feasibility of NO clamp technique for human NO research"Hypertens Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueda S, et al.: "Increased Angiotensin(1-7) concentration after either acute or chronic treatment with ACE inhibitors in patients with essential Hypertension."Hypertens. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimabukuro M, et al.: "Hypoadiponectinemia is closely linked to endothelial dysfunction in man."J Clin Endocrinol Metab.. 88. 3236-3240 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wada A, et al.: "Angiotensin II attenuates the vasodilating effect of a nitric oxide donor, glyceryl trinitrate. Roles of superoxide and angiotensin II type1 receptors."Clin Pharmacol Ther. 36. 440-447 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueda S, et al.: "Angiotensin(1-7) potentiates bradykinin-induced vasodilatation in man."J Hypertens. 19. 2001-2009 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasunari K et al.: "Effects of carvedilol on oxidative stress in poldymorphonuclear and mononuclear cells in patients with essential hypertension."Am J Med.. 116. 460-465 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueda S, et al.: "Validity and feasibility of NO clamp technique for human NO research"Hypertens Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueda S, et al.: "Angiotensin(1-7) concentration after either acute or chronic treatment with ACE inhibitors in patients with essential Hypertension."Hypertens. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasunari K et al.: "Converting enzyme inhibitor temocaprilat prevents high glucose-mediated suppression of human aortic endothelial cell proliferation."J Cardiovasc Pharmacol. 42. S55-S60 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Maeda K et al.: "Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats."Hypertens Res. 26(12). 999-1006 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasunari K et al.: "Dopamine as a novel anti-migration factor of vascular smooth muscle cells through D1A and D1B receptors."J Cardiovasc Pharmacol. 41. S33-S38 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimabukuro M et al.: "Hypoadiponectinemia is closely linked to endothelial dysfunction in man."J Clin Endocrinol Metab. 88(7). 3236-3240 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimajiri Y et al.: "PAX4 mutation (R121W) as a prodiabetic variant in Okinawans."Biochem Biophys Res Commun. 302(2). 342-344 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimabukuro M, Ueda S et al.: "Hypoadiponectinemia is closely linked to endothelial dysfunction in man"J Clin Endocrinol Metab. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wada A, Ueda S et al.: "Angiotensin II attenuates vasodilating effect of NO donor, Glyceryl trinitrate : Roles of superoxide and angiotensin II type 1 receptor"Clin Pharmacol Ther. 71. 440-447 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Ueda et al.: "Angiotensin (1-7) potentiates braclykinin-induceci vasodilatation in man"Journal of Hypertension. 19. 2001-2009 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 和田篤, 植田真一郎, 梅村敏: "ACE阻害薬およびカルシウム拮抗薬のヒト抵抗血管内皮機能への32:219S-220S"臨床薬理. 32. 219-220 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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