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2005 Fiscal Year Final Research Report Summary

Role of active nitrogen oxide in cell stretch-induced pulmonary alveolar injury.

Research Project

Project/Area Number 16590768
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKANAZAWA MEDICAL UNIVERSITY

Principal Investigator

SATOGA Hirohi  KANAZAWA MEDICAL UNIVERSITY, DEPARTMENT OF MEDICINE, PROFESSOR, 医学部, 教授 (90142554)

Co-Investigator(Kenkyū-buntansha) UEDA Yoshimichi  KANAZAWA MEDICAL UNIVERSITY, DEPARTMENT OF MEDICINE, PROFESSOR, 医学部, 教授 (50271375)
Project Period (FY) 2004 – 2005
Keywordscell stretch / ventilator-induced lung injury / pulmonary alveolar epithelial cell / active nitrogen oxide / inducible nitric oxide synthase / broncho-alveolar lavage
Research Abstract

When rats were ventilated with a tidal volume of 30 ml/kg body weight and a PEEP of 0 cmH_2O, ventilator-induced lung injury (VILI) was induced, which was characterized by neutrophil infiltration into alveoli and retention of alveolar fluid. Pretreatment with endotoxin (LPS, 1 mg/kg body weight) augmented VILI. Both NO_2 and NO_3 concentrations in broncho-alveolar lavage fluid (BALF) from VILI lungs were significantly higher than those from spontaneous breathing or a tidal volume of 10 ml/kg body weight.
Pretreatment with ONO-1714, a specific inducible nitric oxide synthase (iNOS) inhibitor, attenuated VILI in a dose-dependent manner ; both neutrophil count and NO_2/110_3 concentrations in BALF were significantly decreased compared with untreated VILI.
Pretreatment with superoxide dismutase (SOD) did not change histopathological findings of VILI significantly, however, both neutrophil count and NO_2/NO_3 concentrations of BALF tended to be reduced compared with untreated VILI.
Expression of both iNOS protein and iNOS mRNA were augmented in VILI compared with control lungs.
Alveolar type II cells (type II cells) were isolated from rat lungs, and a pressure of 30-50 cmH_2O at a rate of 15 times/min for 3 hours was applied on those type II cells. NO_2/NO_3 concentrations in supernatant of cultured type II cells were significantly elevated in response to pressure load. Frequency of apoptosis of pressure-loaded type II cells was significantly increased and activation of NF-κB was significantly augmented compared with untreated type II cells.
Pretreatment of type II cells with ONO-1714 significantly inhibited increment of apoptosis and tended to attenuate activation of NF-κB induced by pressure load.
These results indicated that expression of iNOS and subsequent NO_2/NO_3 production were involved in lung injury induced by cell stretch and/or deformity.

  • Research Products

    (19 results)

All 2006 2005 2004

All Journal Article (19 results)

  • [Journal Article] Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine.2006

    • Author(s)
      Sakuma T, Toga et al.
    • Journal Title

      Crit Care Med 34

      Pages: 676-681

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Microvessel density : Correlation with ^<18>F-FDG uptake and prognostic impact in lung adenocarcinomas.2006

    • Author(s)
      Guo JF, Toga H et al.
    • Journal Title

      J Nucl Med 47

      Pages: 419-425

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Fluorodeoxy- glucose uptake correlates with the growth pattern of small peripheral pulmonary adenocarcinoma.2006

    • Author(s)
      Sagawa M, Toga H et al.
    • Journal Title

      Surg Today 36

      Pages: 230-234

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Denopamine stimulates alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator in rat lungs.2006

    • Author(s)
      Gu XG, Toga H et al.
    • Journal Title

      Respirology 11

      Pages: 566-571

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pulmonary surfactant transport in alveolar type II cells.2006

    • Author(s)
      Osanai K, Toga H et al.
    • Journal Title

      Respirology 11

      Pages: S70-S73

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine.2006

    • Author(s)
      Sakuma T, Toga H, et al.
    • Journal Title

      Crit Care Med 34

      Pages: 676-681

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Microvessel density : Correlation with 18F-FDG uptake and prognostic impact in lung adenocarcinomas.2006

    • Author(s)
      Guo JF, Toga H, et al.
    • Journal Title

      J Nucl Med 47

      Pages: 419-425

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Fluorodeoxy-glucose uptake correlates with the growth pattern of small peripheral pulmonary adenocarcinoma.2006

    • Author(s)
      Sagawa M, Toga H, et al.
    • Journal Title

      Surg Today 36

      Pages: 230-234

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Denopamine stimulates alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator in rat lungs.2006

    • Author(s)
      Gu XG, Toga H, et al.
    • Journal Title

      Respirology 11

      Pages: 566-571

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pulmonary surfactant transport in alveolar type II cells.2006

    • Author(s)
      Osanai K, Toga H, et al.
    • Journal Title

      Respirology 11

      Pages: S70-S73

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression and characterization of Rab38,a new member of the Rab small G protein family.2005

    • Author(s)
      Osanai K, Toga H et al.
    • Journal Title

      Biol Chem 386

      Pages: 143-153

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Catecholamine clearance from alveolar spaces of rat and human lungs.2005

    • Author(s)
      Sakuma T, Toga et al.
    • Journal Title

      Respiration 72

      Pages: 189-196

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression and characterization of Rab38, a new member of the Rab small G protein family.2005

    • Author(s)
      Osanai K, Toga H, et al.
    • Journal Title

      Biol Chem 386

      Pages: 143-153

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Catecholamine clearance from alveolar spaces of rat and human lungs.2005

    • Author(s)
      Sakuma T, Toga H, et al.
    • Journal Title

      Respiration 72

      Pages: 189-196

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Uridine 5'-triphosphate stimulates alveolar fluid clearance in the isolated rat lungs.2004

    • Author(s)
      Sakuma T, Toga H et al.
    • Journal Title

      J Pharmacol Sci 95

      Pages: 420-425

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of CXC chemokines in ventilator- induced lung injury in rats.2004

    • Author(s)
      Toga H, et al.
    • Journal Title

      J Jpn Med Soc Biol Interface 35

      Pages: 9-16

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of α_1-,β_1-,β_2-,β_3-adrenergic agonists on alveolar fluid clearance in isolated rat lungs.2004

    • Author(s)
      Gu X, Toga H et al.
    • Journal Title

      J Kanazawa Med Univ 29

      Pages: 91-96

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Uridine 5'-triphosphate stimulates alveolar fluid clearance in the isolated rat lungs.2004

    • Author(s)
      Sakuma T, Toga H, et al.
    • Journal Title

      J Pharmacol Sci 95

      Pages: 420-425

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of α1-, β1-, β2-, β3-adrenergic agonists on alveolar fluid clearance in isolated rat lungs.2004

    • Author(s)
      Gu X, Toga H, et al.
    • Journal Title

      J Kanazawa Med Univ 29

      Pages: 91-96

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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