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Role of nitric oxide in the regulation of hepatic microcirculation under surgical stress

Research Project

Project/Area Number 07671416
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionOSAKA CITY UNIVERSITY

Principal Investigator

KUBO Shoji  Osaka City University, Medical School, Assistant, 医学部, 助手 (80221224)

Co-Investigator(Kenkyū-buntansha) INOUE Masayasu  Osaka City University, Medical School, Professor, 医学部, 教授 (80040278)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsNitric Oxide / Nucleotides / Portal pressure / Sinusoidal endotherlial cell / Cytochrome p450 / Glutathione / Hepatic microcirculation / チトクロームP450 / 管微小循環 / Nitric oxide
Research Abstract

Some nucleotides bind to purine receptors on cultures stellate cells, increase intracellular calcium concentration, enhance the metabolism of inositol phosphate, and induce contraction of these cells. Adenosine, AMP,ADP and ATP induced relaxation of the contraced mesenteric artery. Such relaxation of aorta and mesenteric artery induced by the nucleotides was significantly inhibited by L-nitro-arginine, a NO synthetase minhibitor, indcating the involvement of NO and/or its metabolites in nucleotide-induced relaxation of these arteries. NO was generated by No synthetase in simusoidal endtherial cells. Contraction and relaxation of the constituent cells of porto-sinusoidal walls might be regulated by these ligands in a concerted mechanism.
Kinetic analysis showed that administration of lipopolysaccharide (LPS) dose-dependently increased the iNOS and NO generation in the liver. ESR analysis revealed that significant amounts of NO-Hb appeared in the circulating RBC,peaked at 8 hr after LPS administration and decreased thereafter with concominant changes in plasma nitrite and nitrate (No_X). ESR signal responsible for heme-iron nitrosyl complexes was also found in the liver of endotoxemic rats. NO may affect celular metabolism by modulating ferrous enzymes. N^G-iminoethyl-L-ornithine, a potent inhibitor of NOS,inhibited the generation of No, NO-Hb, heme-iron nitrosyl complexes and No_X. Administration of LPS decreased the glutathione levels in plasma and bile, whereas it decreased the hepatic level slightly. N^G-nitro-L-arginene, a NO synthase inhibitor, inhibited the LPS-induced decrease of glutathione in plasma and bile. These findings showed that NO plays important roles in the pathogenesis of endotoxin shock and multiple organ failure.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] 池田一雄他: "ラット肝Kupffer細胞におけるNitric Oxide産生機構" 薬理と治療. 23. 153-155 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takemura S.et al: "Dynamic aspects and role of nitric oxide in endotoxin-indual liver injury" Eudtielcam. 3. 99 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 竹村茂一他: "エンドトキシン病態と一酸化窒素代謝の解析" 磁気共鳴と医学. 7. 202-206 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 南山幸子他: "NO-HbからみたNO代謝動態と体内制御機構" 磁気共鳴と医学. 7. 207-210 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 竹村茂一他: "エンドトキシン肝障害における一酸化窒素の役割" 薬理と治療. 24. 31-34 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Minamiyama Y.et al: "Dynamic aspects of glutathione and nitric oxide metabilisne in endotuxeiric rats" Am J Physiol. 271. G575-G581 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue M.et al: "Methods in enzymology" Dynamic aspects of nitric oxide metabolism in the airculation and tissue,6 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takemura S,et al: "Dynamic aspects and role of nitric oxide in endotoxin-induced liver injury" Endthelium. 3. 99 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takemura S,et al: "Dynamic aspect of nitric oxide metabolism in endotoxemic rat." Magnetic Resonance in Medicine. 7. 202-206 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Minamiyama Y,et al: "Effect of thiol status on the formation of nitrosyl-hemoglobin in the circulating erythrocytes." Magnetic Resonance in mMedicine. 7. 207-210 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takemura S,et al: "Role of nitric oxide in endotoxin-induced hepatic injury" Jpn Pharmacol Ther. 24. 31-34 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Minamiyama Y,et al: "Dynamic aspcts of glutathione and nitric oxide metabolism in endotoxemic rats" Am J Physiol. 271. G575-G581 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Minamiyama Y,et al: "Albumine is an important vascular tonus regulator as a reservoir of nitric oxide." Biochim Biophys Res Commun. 225. 112-115 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kawada N,et al: "Pathophysiology of acute obstructive cholangitis." J Hep Bil Pancr Surg. 3. 4-8 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Inoue M,et al: Dynamic aspects of nitric oxide metabolism in the circulation and tissues.Methods in enzymology, Abelson JN,Simon MI,Division of Biology, Calfornia institute of technology.,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 池田一雄,他: "ラット肝Kupffer細胞におけるNitric Oxide産生機構" 薬理と治療. 23. 153-155 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takemura S. et al: "Dynamic Aspects and role of nitric oxide in endotoxin-induced liver injury" Endothelium. 3. 99 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 竹村茂一,他: "エンドトキシン病態と一酸化窒素代謝の解析" 磁気共鳴と医学. 7. 202-206 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 南山幸子,他: "NO-H6からみたNO代謝動態と体内制御機構" 磁気共鳴と医学. 7. 207-210 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 竹村茂一,他: "エンドコキシン肝障害における一酸化窒素の役割" 薬理と治療. 24. 31-34 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Minamiyama Y, et al: "Dynamic aspect of glutathione and nitric oxide metabolism in endotoxemic rats" Am J Physiol. 271. G575-G581 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inoue M. et al: "Methods in enzymology" Dynamic aspects of nitric oxide methabolism in the circulation and tissues, 6 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takemura S.Kinoshita H.Hirohashi K.Kubo S.Kawada N.Inoue M.: "Effect of nucleoides on the contraction of stellate cells" Cells of hepatic simusoid. 5. 354-357 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takemura S.Kawada N.Minamiyama Y.Inoue M.Kubo S.Hirohashi K.Kinoshita H.: "Role of stellate cells in the regulation of hepatic microcirculation" Microcirculation annual. 10. 117-118 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kubo S.Rodngues I Jr et al.: "Stimulation of phagocytic activity of murine kupffer cells by tuftsin" Hepatology. 19. 1044-1049 (1994)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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