1997 Fiscal Year Final Research Report Summary
Role of endogenous nitric oxide (NO) on hypoxic pulmonary vasoconstriction and ventilation/perfusion mismatching
| Project/Area Number |
08670643
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
NAKANO Hitoshi Asahikawa Medical College, Medicine, Instructor, 医学部, 助手 (40221452)
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| 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)
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| Project Period (FY) |
1996 – 1997
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| Keywords | exhaled nitric oxide / NO metabolites / pulmonary circulation / isolated perfused lung / hypoxic pulmonary vasoconstriction / hemoglobin concentration / hypoxia / airway epithelia |
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| 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.
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