Airway constriction by xanthine/xanthine oxidase in guinea pigs in vivo.
Reactive oxygens are considered to be one of the mediators involved in inflammation. We investigated the constrictive effects of reactive oxygens generated by aerosolized xanthine/xanthine oxidase (XOD) on the airways of anesthetized guinea pigs. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of xanthine (1.0 M)/XOD (10, 15 U/ml) caused a significant increase in VO. This airway constriction tended to be enhanced by pretreatment with inhaled superoxide dismutase, but was suppressed by inhaled catalase. Inhalation of hydrogen peroxide caused an airway constriction in a concentration-dependent manner (0.1-2.0 M). Xanthine/XOD significantly enhanced the maximal change in VO after inducing airway inflammation by SO2 exposure. The pretreatment with inhalation of xanthine/XOD did not affect the airway constriction induced by inhaled histamine. However, in SO2-exposed guinea pigs, the inhalation of xanthine/XOD significantly increased the sensitivity to histamine. These results indicate that hydrogen peroxide and other reactive oxygen intermediates produced by xanthine/XOD may cause an airway constriction and airway hyperresponsiveness.
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
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Misawa
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Nakano
D000280:Administration, Inhalation; D000336:Aerosols; D000402:Airway Obstruction / Q000139:chemically induced*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D002374:Catalase / Q000633:toxicity; D003251:Constriction, Pathologic / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D012137:Respiratory System / Q000187:drug effects*; D013458:Sulfur Dioxide / Q000633:toxicity; D013482:Superoxide Dismutase / Q000633:toxicity; D019820:Xanthine; D014969:Xanthine Oxidase / Q000008:administration & dosage / Q000633:toxicity*; D014970:Xanthines / Q000008:administration & dosage / Q000633:toxicity*
D000336:Aerosols; D014970:Xanthines; D013458:Sulfur Dioxide; D019820:Xanthine; D006632:Histamine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase