Markedly Increased Nasal Blockage by Intranasal Leukotriene D_4 in an Experimental Allergic Rhinitis Model: Contribution of Dilated Mucosal Blood Vessels
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概要
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We examined whether nasal hyperresponsiveness to leukotriene (LT) D4 is seen in our allergic rhinitis model, which showed sneezing and biphasic nasal blockage by repeated antigen inhalation challenge, and whether a dilatation of mucosal blood vessels contributes to this hyperresponsiveness. Nasal blockage [increase of specific airway resistance (sRaw)] was indexed as nasal (hyper)responsiveness. The sensitized – challenged guinea pig showed a remarkable dose-dependent increase in sRaw by intranasal instillation of LTD4 (10 μl/nostril) at 10−10 to 10−6 M 10 h and 2 days but not 7 days after the challenge. The increase in sRaw induced by LTD4 was largely blocked by pranlukast or naphazoline, and this was dose-dependently suppressed by Nω-nitro-L-arginine methyl ester. Sodium nitroprusside induced an elevation of sRaw in the sensitized – challenged animal in the hyperresponsiveness state, but the degree did not differ from that in the non-sensitized – non-challenged group. The amount of NO2− and NO3− in nasal cavity lavage fluid after LTD4 instillation in the sensitized – challenged animal in the hyperresponsiveness state was significantly greater than that before the instillation. These results demonstrate that the hyperresponsiveness to LTD4 acquired by repeated antigen challenge is mainly due to dilatation of nasal blood vessels, which can be related to hyperproduction of nitric oxide through cysteinyl LT1-receptor activation.
- 社団法人 日本薬理学会の論文
- 2001-06-01
著者
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TAKENAKA Hiroshi
Department of Earth and Planetary Sciences, Kyushu University
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Sugahara Yazuyuki
Dep. Of Lab. Medicine Nagasaki Univ. Graduate School Of Biomedical Sciences Nagasaki Univ. Hospital
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Imai Aki
Department Of Discovery Biology Research Global Research & Development Nagoya Laboratories Pfize
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Imai Aki
京都薬科大学 薬理
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Imai Aki
Department Of Pharmacology Kyoto Pharmaceutical University
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Mizutani Nobuaki
Department of Pharmacology, Kobe Pharmaceutical University, Japan
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NABE Takeshi
Department of Pharmacology, Kyoto Pharmaceutical University
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KOHNO Shigekatsu
Department of Pharmacology, Kyoto Pharmaceutical University
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SAKURAI Hiromu
Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University
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Takenaka Hiroshi
Department Of Otolaryngology Osaka Medical College
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Takenaka Hiroshi
Department Of Otorhinolaryngology Osaka Medical College
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Nabe Takeshi
Department Of Pharmacology Kyoto Pharmaceutical University:department Of Pneumology Ogaki Municipal
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Nabe Takeshi
Department Of Pharmacology Kyoto Pharmaceutical University
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Takenaka H
Kyushu Univ.
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Takenaka Hiroshi
Department Of Earth And Planetary Sciences Kyushu University
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Kohno Shigekatsu
Department Of Pharmacology Division Of Pathological Sciences Kyoto Pharmaceutical University
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Mizutani Nobuaki
Department Of Pharmacology Kobe Pharmaceutical University
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Takenaka Hiroshi
Department Of Chemistry Faculty Of Science Osaka City University
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Sakurai Hiromu
Analytical And Bioinorganic Chemistry Kyoto Pharmaceutical University
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Nabe T
Department Of Pharmacology Kyoto Pharmaceutical University
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