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1997 Fiscal Year Final Research Report Summary

Role of endogenous nitric oxide (NO) on hypoxic pulmonary vasoconstriction and ventilation/perfusion mismatching

Research Project

Project/Area Number 08670643
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionAsahikawa Medical College

Principal Investigator

NAKANO Hitoshi  Asahikawa Medical College, Medicine, Instructor, 医学部, 助手 (40221452)

Co-Investigator(Kenkyū-buntansha) HASEBE Naoyuki  Asahikawa Medical College, Medicine, Associate Professor, 医学部, 講師 (30192272)
IWAMOTO Jun  Asahikawa Medical College, Physiology, Associate Professor, 医学部, 助教授 (20160137)
Project Period (FY) 1996 – 1997
Keywordsexhaled nitric oxide / NO metabolites / pulmonary circulation / isolated perfused lung / hypoxic pulmonary vasoconstriction / hemoglobin concentration / hypoxia / airway epithelia
Research Abstract

We measured pulmonary arterial pressure (Ppa), the concentration of exhaled NO (ex NO) and the accumulation of perfusate NO_2^-/NO_3^- (NO_x) in the isolated perfused rabbit lungs.
1.The exNO from the buffer-perfused lungs decreased along with a increase in hematocrit with a hyperbolic fashion. Pulmonary blood flow did not affect the hematocrit-dependent decrease of exNO.These results suggest that exNO from the lung is cleared via the pulmonary blood for the physiological range of hematocrit. Therefore, the values of exNO which we measured is masked by circulating pulmonary blood and does not reflect the correct production of NO from the lung.
2.A bolus injection of acetylcholine into the pulmonary artery evoked a transient increase of exNO with a decrease of Ppa while the NO_x remained unchanged. The step increase of flow caused corresponding elevation of the production rate of exNO,whereas NO_x did not change. L-NMMA caused a fall of exNO and NO_x with a rise of Ppa in the range of all flow rate. The pulmonary vascular conductance progressively increased along with flow rate in control state. However, L-NMMA blocked the flow-dependent increase of the conductance. These results suggest that flow-dependent increase of exNO is associated with pulmonary capillary recruitment.
3.The exNO was gradually decreased along with a reduction of O_2 concentration and changing to normoxia exhibited a prompt increase of exNO.Decreasing O_2 tension reduced exNO curvilineally. This curvilinearl relationship between O_2 tension and exNO is similar to that between substrate concentration and enzyme-reaction velocity (Michaelis-Menten kinetics). We have demonstrated the exNO is synthesized enzymatically by using ambient oxygen as a substrate. This result suggests that epithelial NO synthesis itself may function as an 'oxygen sensor' in the airway and NO produced in the epithelium may play an important role in pulmonary pathophysiology.

  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Ogasa, Toshiyuki.: "Blood attenuates flow-dependent increase in exhaled NO in buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.153(4). A186 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakano, Hitoshi.: "Hypoxia decreases exhaled NO in isolated buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.153(4). A186 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwamoto, Jun.: "Analysisu of single breath nitric oxide (SBVNO) in healthy subujects." FASEB J.11(3). A346 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogasa, Toshiyuki.: "Flow-induced production of endothelial nitricoxide in buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.155(4). A824 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogasa, Toshiyuki: "Blood attenuates flow-dependent increase in exhaled NO in buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.153 (4). A186 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano, Hitoshi: "Hypoxia decreases exhaled NO in isolated buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.153 (4). A186 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwamoto, Jun: "Anslysis of single breath nitric oxide (SBVNO) in healthy subjects." FASEB J.11 (3). A346 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogasa, Toshiyuki: "Flow-induced production of endothelial nitric oxide in buffer-perfused rabbit lungs." Am.J.Resp.Crit.Care Med.155 (4). A121 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano, Hitoshi: "Analysis of exhaled NO and carbon dioxide in patients with COPD." Am.J.Resp.Crit.Care Med.155 (4). A824 (1997)

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

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Published: 1999-03-16  

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