Studies fro the role of nitric oxide in bronchial asthma
| Project/Area Number |
09670618
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
AIZAWA Hisamichi Kyushu University, Research Institute for Diseases of the Chest, Associate Professor, 医学部, 助教授 (90175711)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Makoto Kyushu University, Research Institute for Diseases of the Chest, Clinical Staff, 医学部, 医員 (90315060)
INOUE Hiromasa Kyushu University, Research Institute for Diseases of the Chest, Assistant Professor, 医学部, 助手 (30264039)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | nitric oxide (NO) / airway responsiveness / airway inflammation / asthma / L-NAME / 気管支喘息 / 気道過敏性 / NO / i-NANC / 好酸球 / ピークフロー / 誘発喀痰 / 吸入ステロイド |
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| Research Abstract |
We studied the role of nitric oxide (NO) in the regulation of airway responsiveness in anesthetized and mechanically ventilated cats. To assess airway responsiveness, we measured the changes in total pulmonary resistance (RL) produced by delivering serotonin aerosol to the airways before and after Nw-nitro-L-arginine methyl ester (L-NAME), or ganglionic blocker, hexamethonium which was reported to block I-NANC. Serotonin was chosen because it causes bronchoconstriction in part by neural reflex. To further clarify the mechanism (s) involved, we also determined the effect of inhaled capsaicn in the animals with sustained bronchoconstriction induced by serotonin after treatment with atropine and propranolol. Inhibition of NO synthase by L-NAME or blockade of I-NANC neurons by hexamethonium significantly increased airway responsiveness. However, addition of L-NAME did not further increase airway responsiveness in animals treated with hexamethonium. In the presence of atropine and propranol
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ol, inhaled capsaicin caused a marked bronchodilation during serotonin-induced sustained bronchoconstriction. The bronchodilation induced by capsaicin was significantly suppressed by hexamethonium or by L-NAME. These results suggest that the NO released from I-NANC neurons is important in modulating the airway responsiveness of cats in vivo.
On the other hand, NO is increased in exhaled air of asthmatics. We hypothesized that endogenous NO contributes to airway inflammation and hyperresponsiveness, and that interleukin-8 (IL-8) might be involved in this mechanism. In human transformed bronchial epithelial cells in vitro, NO donors increased IL-8 production dose-dependently. In addition, tumor necrosis factor-a plus IL-1b plus interferon-g increased IL-8 in culture supernatant of epithelial cells ; the combination of NO synthase inhibitors, aminoguanidine plus NG-nitro-L-argiine methyl ester (L-NAME), attenuated the cytokines-induced IL-8 production in epithelial cells. In guinea pigs in vivo, ozone exposure induced airway hyperresponsiveness to acetylcholine and increased neutrophils in bronchoalveolar lavage fluid, and these changes were persisted for at least 5 h. Pretreatment with NO synthase inhibitors had no effect on airway hyperresponsiveness or neutrophil accumulation immediately after ozone, but significantly inhibited the changes 5 h after ozone. NO synthase inhibitors also attenuated the increases of nitrite/nitrate levels in bronchoalveolar lavage fluid and the IL-8 mRNA expression in epithelial cells and in neutrophils in guinea pig airways 5 h after ozone. These results suggest that endogenous NO may play an important role in the persistent airway inflammation and hyperresponsiveness after ozone exposure, presumably partly through the upregulation of IL-8. Less
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Report
(3 results)
Research Products
(15 results)
