Nobuaki Mizutani1, Takeshi Nabe1, Aki Imai1, Hiromu Sakurai2, Hiroshi Takenaka3 and Shigekatsu Kohno1,*
1Department of Pharmacology and 2Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, Japan
3Department of Otorhinolaryngology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan
*Corresponding author. FAX: +81-75-595-4764, E-mail: kohno@mb.kyoto-phu.ac.jp
Abstract: 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 SUPed as nasal (hyper)responsiveness. The sensitized - challenged guinea pig showed a remarkable dose-dependent increase in sRaw by intranasal instillation of LTD4 (10 ml/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 Nw-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.
Keywords: Hyperresponsiveness, Allergic rhinitis, Leukotriene D4, Nasal blockage, Nitric oxide
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