Roles of nitric oxide and neuropeptides in the development of lung injuries induced by chemical irritants.
| Project/Area Number |
08670401
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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 |
Hygiene
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| Research Institution | Keio University |
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Principal Investigator |
OMAE Kazuyuki Keio University School of Medicine Associate Professor, 医学部, 助教授 (60118924)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEBAYASHI Toru Keio University School of Medicine Assistant Professor, 医学部, 専任講師 (30265780)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | ozone / nittric oxide / neuropeptide / substance P / neurokinin A / airway responsiveness / サブスタンスP / ニューロキニンA |
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| Research Abstract |
Inhalation studies were performed to examine roles of neuropeptides and nitric oxide in airway responses to ozone in rats or mice.
1.Role of neuropeptides
The purpose of this study was to determine whether tachykinins mediate the protective effects of C-fibers against ozone (O_3) exposure. Male Sprague-Dawley rats were exposed to 1ppm O_3 or air for three hours. Two hours later airway responsiveness to inhaled methacholine was measured and a bronchoalveolar lavage (BAL) was performed. Rats were treated with the selective NK_1 and NK_2 receptor antagonist, either throughout the O_3 exposure and methacholine challenge or just before the methacholine challenge. The effect of neonatal capsaicin pretreatment, which ablates C-fibers, on O_3-induced changes in BAL cells and protein was also examined. Pretreatment of rats with the antagonists during O_3 exposure significantly augmented influx of neutrophils into the lung and airways and shedding of epithelial cells. Pretreatment of rats with the
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antagonists after the O_3 exposure had no effect on BAL cell recovery. Neither treatment had any effect on baseline pulmonary mechanics or airway responsiveness. Neonatal capsaicin pretreatment. which ablates C-fibers, also resulted in increased BAL neutrophils and protein after O_3 compared to vehicle treated rats. These results suggest that tachykinins mediate protective effects of C fibers against O_3-induced lung injury, but are not involved in attenuating the development of airway hyperresponsiveness.
2.Role of nitric oxide
The purpose of this study was to examine whether nitric oxide mediate airway responses to O_3. Male ICR mice with/without N-Nitro-Arginine (NOARG,100mg/kg) were exposed to 1ppm O_3 or air for four hours. Twenty-four hours later a bronchoalveolar lavage (BAL) was performed. Number of neutrophils in BAL fluid was decreased in the O_3/NOARG group, which indicated nitric oxide might relate to development of O_3 induced-airway inflammation. We further evaluated the role of nitric oxide in O_3-induced airway hyperresponsiveness, but no clear relationship was observed. Less
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Report
(3 results)
Research Products
(6 results)
