Involvement of peroxynitrite in pollen-induced nasal blockage in guinea pigs.
Nitric oxide (NO) has been implicated in early and late phase nasal blockage in a Japanese cedar pollen-induced experimental allergic rhinitis guinea pig model. In this study, we investigated the role of peroxynitrite, which is formed by a rapid reaction of NO with superoxide anion, in the antigen-induced biphasic nasal blockage. Sensitized guinea pigs were repeatedly challenged by pollen inhalation once every week. The peroxynitrite scavenger, ebselen (30 mg/kg), or the xanthine oxidase inhibitor, allopurinol (50 mg/kg), was intraperitoneally administered 30 min before the antigen challenge. The late phase nasal blockage induced 4 h after the challenge was largely suppressed by ebselen (57% inhibition; P<0.05) and allopurinol (47% inhibition; P<0.05), but neither ebselen nor allopurinol influenced the early phase response. On the other hand, the intranasal instillation of peroxynitrite (10(-3) and 10(-2) M, 10 microl/nostril) caused a remarkable dose-dependent nasal blockage in the sensitized guinea pig. These results suggest that peroxynitrite plays a major role in the late phase nasal blockage induced by the antigen challenge in sensitized guinea pigs.
Mizutani
Nobuaki
N
Department of Pharmacology, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
Nabe
Takeshi
T
Fujii
Masanori
M
Yoshino
Shin
S
Kohno
Shigekatsu
S
D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000493:Allopurinol / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology; D032485:Cryptomeria / Q000276:immunology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D054833:Isoindoles; D017998:Leukotriene D4 / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015508:Nasal Obstruction / Q000276:immunology* / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016566:Organoselenium Compounds / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology / Q000502:physiology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000503:physiopathology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000485:Allergens; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D030421:Peroxynitrous Acid; C042986:ebselen; D000493:Allopurinol; D017998:Leukotriene D4; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D019331:NG-Nitroarginine Methyl Ester