2002 Fiscal Year Final Research Report Summary
NEW STRATEGY BASED ON REGULATION OF OXTPATIVE STRESS IN TREATMENT OF BRONCHIAL ASTHMA
| Project/Area Number |
13670611
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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 | Osaka City University |
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Principal Investigator |
KANAZAWA Hiroshi OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 大学院・医学研究科, 助手 (90332957)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Kazuto OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究科, 助教授 (50173232)
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| Project Period (FY) |
2001 – 2002
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| Keywords | NITRIC OXIDE / AIRWAY HYPERREACTIVITY / β_2-ADRENQCEPTOR AGONIST / AIRWAY INFLAMMATION |
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| Research Abstract |
We have previously found that higher levels of nitrogen oxides in exhaled air and in induced sputum were found in asthmatics compared to normal control subjects, and that nitrogen oxides altered β_2 -adrenoceptor (β_-AR) function in an experimental animal model. Therefore, this study was designed to determine whether nitrogen oxides influence the bronchodilating activity of β_2-AR agonists in asthmatic patients. We simultaneously measured the levels of nitrogen oxides in exhaled air and in induced sputum in 20 asthmatic patients. The bronchodilating activity of β_2-AR agonists was expressed as a spontaneous recovery (pre- raethacholine) and recovery from the lowest value in FEV1 evoked by methacholine challenge (post-methacholine). For 1-week after the first study, 400 μg of beclomethasone dipropionate (BDP) twice daily was administered for all patients, and the above mentioned protocols were repeated. Recovery in FEV1 (pre-methacholine) after β_2-AR agonists was not significantly correlated with any baseline FEV1 and PC20 methacholine. Moreover, recovery in FEV1 (post-methacholine) after β_2-AR agonists was not also significantly correlated with maximal fall in FEV1 after methacholine challenge and PC20 methacholine. However, recovery in FEV1 after β_2-AR agonists was inversely correlated with NO levels in exhaled air, and concentration of nitrite and nitrate in induced sputum. After treatment with inhaled BDP for 1-week, there was no significant change in baseline FEV1. However, there was a significant decrease in the concentration of nitrite and nitrate in induced sputum. We found that change of nitrite and nitrate levels in induced sputum after 1-week BDP therapy was significantly correlated with change in bronchodilating activity of β_2-AR agonists between pre- and post-BDP therapy. We determined that nitrogen oxides in the airways reduced β_2-AR agonists-induced brochodilation in asthmatics.
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