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Involvements of NO and histamine in radiographic contrast medium-induced pulmonary dysfunction

Research Project

Project/Area Number 13672390
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionKyushu University

Principal Investigator

OISHI Ryozo  Kyushu University Hospital, Professor, 医学部附属病院, 教授 (90112325)

Co-Investigator(Kenkyū-buntansha) KATAOKA Yasufumi  Fukuoka Univ., Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70136513)
HONDA Hiroshi  Kyushu University Hospital, Professor, 医学部附属病院, 教授 (90145433)
ITOH Yoshinori  Kyushu University Hospital, Associate Professor, 医学部附属病院, 助教授 (50159927)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsRadiographic contrast medium / Pulmonary dysfunction / Mast cell / Histamine / Tryptase / Endothelial cell / Proteinase-activated receptor-2 / Carbazochrome / proteinase-activated receptor-2 / 抗ヒスタミン薬
Research Abstract

Although radiographic contrast media (RCM) are increasingly used for radiography and magnetic resonance imaging, undesirable actions associated with intravascular injection of RCM such as anaphylactoid adverse reactions and pulmonary dysfunction occur occasionally and no prevention or effective therapy for the adverse events has not been established. The present study was performed to determine the possible mechanisms underlying the RCM-induced pulmonary dysfunction and to propose a useful agent for the cure or prevention of servere adverse reaction to RCM. The research results as follows:
1. RCM causes the degranulation of pulmonary mast cells and resultant release of histamine (HA) that in turn increases vascular permeability by stimulating H_1 and H_2 receptors.
2. A variety of RCM stimulated HA release from rat pulmonary cells, in which the action of ionic RCM was more pronounced than that of non-ionic materials. It was clarified that the decrease in cellular cyclic AMP content and an increase in intracellular Ca^<2+> contributed largely to mast cell HA release induced by ionic RCM.
3. Ioxaglate, an ionic RCM, induces pulmonary dysfunction by stimulating the release of mast cell tryptase. A clinically available nafamostat mesilate is potentially useful for the prevention or cure of anaphylactoid adverse reactions to the intravascular RCM injection.
4. Mast cell tryptase impairs endothelial barrier function through activation of endothelial proteinase-activated receptor-2 in a manner dependent on the phospholipase C activity.
5. Carbazochrome is a potentially useful for the prophylaxis of RCM-induced acute pulmonary adverse events. The stablization of endothelial barrier function may be associated with such a protective action of carbazochrome.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Wakako Furuta et al.: "Contrast media increase vascular endothelial permeability by inhibiting nitric-oxide production"Investigative Radiology. 37. 13-19 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiaki Sendo et al.: "Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats"European Journal of Pharmacology. 450. 203-208 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeshi Goromaru et al.: "Evidence for an involvement of mast cell degranulation and subsequent stimulation of histamine H_1 and H_2 receptors in radiographic contrast media-increased vascular permeability in rats"Naunyn-Schmiedebergs Archives of Pharmacology. 366. 605-612 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomoko Sumimura et al.: "Calcium-dependent injury of human microvascular endothelial cells induced by a variety of iodinated radiographic contrast media"Investigative Radiology. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mami Saito et al.: "Roles of intracellular Ca^<2+> and cyclic AMP in mast cell histamine release induced by radiographic contrast media"Naunyn-Schmiedebergs Archives of Pharmacology. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiaki Sendo et al.: "A potent tryptase inhibitor nafamostat mesilate dramatically suppressed pulmonary dysfunction induced in rats by a radiographic contrast medium"British Journal of Pharmacology. 138. 959-967 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Toshiaki Sendo et al.: "Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells"Cellular Signalling. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naoko Sakai et al.: "Delayed adverse reactions to iodinated radiographic contrast media after coronary angiography : A search for possible risk factors"Journal of Clinical Pharmacy and Therapeutics. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] W. Furuta et al.: "Contrast media increase vascular endothelial permeability by inhibiting nitric oxide production"Investigative Radiology. 37(1). 13-19 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Sendo et al.: "Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats"European Journal of Pharmacology. 450(2). 203-208 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Goromaru et al.: "Evidence for an involvement of mast cell degranulation and subsequent stimulation of histamine H_1 and H_2 receptors in radiographic contrast media-increased vascular permeability in rats"Naunyu-Schmiedeberg's Archives Pharmacology. 366(6). 605-612 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Sumimura et al.: "Calcium-dependent injury of human microvascular endothelial cells induced by a variety of iodinated radiographic contrast media"Investigative Radiology. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Saito et al.: "Roles of intracellular Ca^<2+> and cyclic AMP in mast cell histamine release induced by radiographic contrast media"Naunyu-Schmiedeberg's Archives Pharmacology. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Sendo et al.: "A potent tryptase inhibitor nafamostat mesilate dramatically suppressed pulmonary dysfunction induced in rats by a radiographic contrast medium"British Journal of Pharmacology. 138(5). 959-967 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Sendo et al.: "Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells"Cellular Signalling. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Sakai et al.: "Delayed adverse reactions to iodinated radiographic contrast media after coronary angiography: A search for possible risk factors"Journal of Clinical Pharmacy and Therapeutics. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wakako Furuta et al.: "Contrast media increase vascular endothelial permeability by inhibiting nitric-oxide production"Investigative Radiology. 37・1. 13-19 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshiaki Sendo et al.: "Carbazochrome attenuates pulmonary dysfunction induced by a radiographic contrast medium in rats"European Journal of Pharmacology. 450・2. 203-208 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takeshi Goromaru et al.: "Evidence for an involvement of mast cell degranulation and subsequent stimulation of histamine H_1 and H_2 receptors in radiographic contrast media-increased vascular permeability in rats"Naunyn-Schmiedebergs Archives of Pharmacology. 366・6. 605-612 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshiaki Sendo et al.: "A potent tryptase inhibitor nafamostat mesilate dramatically suppressed pulmonary dysfunction induced in rats by a radiographic contrast medium"British Journal of Pharmacology. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Toshiaki Sendo et al.: "Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells"Cellular Signalling. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Naoko Sakai et al.: "Delayed adverse reactions to iodinated radiographic contrast media after coronary angiography : A search for possible risk factors"Journal of Clinical Pharmacy and Therapeutics. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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

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