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Development of antihypertensive drugs: L-arginine and its derivatives as a precursor of endothelium-derived relaxing factor

Research Project

Project/Area Number 03557012
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionKEIO UNIVERSITY

Principal Investigator

NAKAKI Toshio  KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PHARMACOLOGY, ASSISTANT PROFESSOR, 医学部, 講師 (30164148)

Co-Investigator(Kenkyū-buntansha) SONAKA Ichiro  AJINOMOTO CO., INC., CENTRAL RESEARCH LABORATORIES, RESEARCHER, 中央研究所, 研究員
SUZUKI Hiromichi  KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, ASSOCIATE P, 医学部, 助教授 (80129494)
SARUTA Takao  KEIO UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, PROFESSOR, 医学部, 教授 (70051571)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 1992: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1991: ¥7,500,000 (Direct Cost: ¥7,500,000)
KeywordsL-arginine / Antihypertensive drug / Nitric oxide / EDRF / Plasma cGMP / Nitrite / nitrate / Citrulline / Endothelium / 原発性アルドステロン症 / 腎血管性高血圧症 / 一酸化窒素(NO)
Research Abstract

Intravenous administration of L-arginine to normotensive healthy volunteers caused a slight reduction of systemic blood pressure. To essential and secondary hypertension it caused a marked decrease in systemic blood pressure. Based on observations of the increase in plasma cyclic GMP and citrulline, as well as urinary nitrite/nitrate and increased output of nitric oxide from cultured endothelial cells, the antihypertensive effect of L-arginine was probably due to an increase in nitric oxide synthesis/release in vivo. L-arginine suppressed plasma aldosterone. These results suggest that exogenous L-arginine produces a vasodilatory effect by increasing NO production and that L-arginine or released NO modulates the release of neuroendocrine hormones in hypertensive subjects.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] HISHIKAWA,K.: "L-arginine-induced hypotension" Lancet. 337. 683-684 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HISHIKAWA,K.: "New method of investigating functional roles of pre-ssure-sensitive mechanoreceptor in human endothelial cells" J.Gardiovasc.Pharmacol.20. S66-S67 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HISHIKAWA,K.: "Effect of systemic L-arginine administration on hemo-dynamics and nitric oxide release in man" Jpn.Heart J.33. 41-48 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HISHIKAWA,K.: "Transmural pressure inhibits nitric oxide release from human endothelial cells" Eur.J.Pharmacol.215. 329-331 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HISHIKAWA,K.: "L-arginine as an antihypertensive agent" J.Gardiovasc.Pharmacol.20. S196-S197 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] SUZUKI,H.: "Increases in NO_2-NO_3- excreation in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure" Clin.Sci.82. 631-634 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] HISHIKAWA,K.: "Role of L-arginine-NO pathway in hypertension" J.Hypertension. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Hishikawa, T. Nakaki, H. Suzuki, T. Saruta and R. Kato: "L-arginine-induced hypotension" Lancet. 337. 683-684 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Hishikawa, T. Nakaki, H. Suzuki, T. Saruta and R. Kato: "New method of investigating functional roles of pressure-sensitive mechanoreceptor in human endothelial cells" J. Cadiovasc. Pharmacol.20. S66-S67 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Hishikawa, T. Nakaki, H. Suzuki, T. Saruta and R. Kato: "Effect of systemic L-arginine administration on hemodynamics and nitric oxide release in man" Jpn. Heart J.33. 41-48 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Hishikawa, T. Nakaki, H. Suzuki, T. Saruta and R. Kato: "Transmural pressure inhibits nitric oxide release from human endothelial cells" Eur. J. Pharmacol.215. 329-331 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Hishikawa, T. Nakaki, H. Suzuki, T. Saruta and R. Kato: "L-arginine as an antihypertensive agent" J. Cardiovasc. Pharmacol.20. S196-S197 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] H. Suzuki, H. Ikenaga, K. Hishikawa, T. Nakaki, R. Kato and T. Saruta: "Increases in NO2^-/NO3^- excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure." Clin Sci. 82. 631-634 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K. Hishikawa, T. Nakaki, H. Suzuki, T. Saruta and R. Kato: "Role of L-arginine-NO pathway in hypertension" J. Hypertension. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hishikawa,K.: "Transmural pressure inhibits nitric oxide release from human endothelial cells" Eur.J.Pharmacol.215. 329-331 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hishikawa,K.: "L-arginine as an antihypertensive agent" J.Cardiovasc.Pharmacol.20. S196-S197 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Suzuki,H.: "Increases in NO_2-/NO_3- excreation in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure" Clin.Sci.82. 631-634 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hishikawa,K.: "Role of L-arginine-NO pathway in hypertension" J.Hypertension. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hishikawa,K.: "L-arginine-induced hypotension" Lancet. 337. 683-684 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hishikawa,K.: "Effect of systemic L-arginine administration on hemodynamic and nitric oxide release in man" Jpn.Heart J.(1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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