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The role of kallikrein inhibitor in the regulation of the renal kallikrein-kinin system activity

Research Project

Project/Area Number 60480235
Research Category

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

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionSapporo Medical University

Principal Investigator

SHIMAMOTO Kazuaki  Sapporo Medical College, Associate Professor, 医学部, 助教授 (40136940)

Co-Investigator(Kenkyū-buntansha) 吉田 茂夫  札幌医科大学, 医学部, 講師 (30136965)
TANAKA Shigemichi  Sapporo Medical College, Assistant Professor, 医学部, 講師 (50163522)
SHOJI Tetsuro  Sapporo Medical College, Assistant Professor, 医学部, 講師 (60154340)
KIKUCHI Kenjiro  Sapporo Medical College, Associate Professor, 医学部, 助教授 (30045455)
YOSHIDA Shigeo  Sapporo Medical College, Assistant Professor
Project Period (FY) 1985 – 1987
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1987: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1986: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1985: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsKallikrein / Kallikrein-inhibitor / Essential Hypertension / Renal Depressor System / Low Renin Essential Hypertension / Chronic Glomerulonephritis / 酵素比活性 / カリクレイン,カリクレイン・インヒビター / 慢性系球体腎炎 / カリクレイン-インヒビター / palyacrylamide gel electrophoreris
Research Abstract

Urinary excretions of kallikrein quantity and activity were significantly lower in patients with both essential hypertension and those with chronic glomerulonephritis. The specific activity calculated from enzyme activity divided by quantity was significantly lower in both patient groups than in the normal control,suggesting that the inhibited activity of renal kallikrein in these diseases may be caused by both the suppression of enzyme production and enzyme activity. Therefore, the possibility was investigated whether the kallikrein inhibitors may have a connection in the mechanism of the suppressed activity of kallikrein. After elution of urine samples in Sephadex G-200 column chromatography,any substance which inhibits the kallikrein activity was not detected in patient samples. Kallikrein activity and quantity revealed a single peak,and other peaks were not found in this study. However,the specific activity in each fractionations represented the significant lower values in the part of early fractionations of peak than in later,but no difference in normal control,suggesting that the kallikrein inhibitor with low molecular weight remains in both diseases. In the study by polyacrylamide gel electrophoresis, (PAGE) and Western Blot analysis,only one band was observed in patient's samples as well as the normal control,and an abnormal band was not detected.
In rat experiments,both urinary excretions of kallikrein quantity and activity were significantly increased and decreased in DOCA-salt hypertension or 5/6 renoprival hypertension,respectively. Howeverthere was no significant difference found in kallikrein specific activity between the normal control and the experimental groups. This data suggests that the kallikrein-inhibitor does not play an important role in the rat kidney and that the regulation of this system activity may be performed mainly in the enzyme production step.

Report

(3 results)
  • 1988 Final Research Report Summary
  • 1987 Annual Research Report
  • 1986 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Iimura.O,et al: Agents and Actions.22. 247-256 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Shimamoto.K,et al: Adv.Exp.Med.Biol.(1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masuda.A,et al: J.Clin.Hypertens.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 尾形仁子 他: 札幌医学雑誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Iimura.O.: "Renal Function,Hypertension and Kallikrein-Kinin System" University of Tokyo Press, 250 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Osamu Iimura, et al.: "The pathophysiological role of renal dopamine,kallikrein-kinin and prostaglandin systems in essential hypertension" Agents and Actions. 22. 247-256 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Kazuaki Shimamoto, et al.: "Physiological role of renal kallikrein-kinin system in human" Adv. Exp. Med. Biol.in press. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hitoko Ogata, et al.: "The pathophysiological role of renal depressor systems in essential hypertensives" Sapporo Medical Journal (Japanese with English Abstract). in preparation.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Atsushi Masuda.: "The studies on the renal kallikrein-inhibitor in the patients with low renin essential hypertension and renoparenchymal hypertension" J.Clin.Hypertens.in preparation.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Osamu Iimura.: Pathophysiological significance of kallikrein-kinin system in essential hypertension. University of Tokyo Press, (1988,in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Iimura,O.et al.: Agents and Actions. 22. 247-256 (1986)

    • Related Report
      1987 Annual Research Report
  • [Publications] Shimamoto,K.et al: Adv.Exp.Med.Biol.in press. (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Masuda,A.es al.: J.Clin.Hypertens.

    • Related Report
      1987 Annual Research Report
  • [Publications] 尾形仁子他: 札幌医学雑誌.

    • Related Report
      1987 Annual Research Report
  • [Publications] Iimura,O: "Renal Function,Hypertension and Kallikrein-Kinin System" University of Tokyo Press, 250 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] 島本和明: 脈管学. 26. 355-360 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] O.Iimura,et al.: Agents and Actions. (1987)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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