<Original Paper>Airway Remodeling in a Guinea Pig Model of Chronic Asthma : Its Influence on Airway Responsiveness and Pharmacological Properties of Airway Smooth Muscle, and Its Prevention by Corticosteroids

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Airway remodeling in bronchial asthma occurs as a result of continuance or repetition of eosinophilic airway inflammation. It has the potential to affect airway responsiveness to nonspecific stimuli and the pharmacological properties of airway smooth muscle, but the direct evidence of this is sparse. It is also unknown whether corticosteroids can prevent the development of airway remodeling. To assess these questions, we made a guinea pig model of chronic asthma that consistently showed airway remodeling and analyzed it not only pathologically but also physiologically and pharmacologically. The effects of the corticosteroid treatment on the development of airway remodeling were also examined. Guinea pigs were sensitized by repeated exposure to aerosolized ovalbumin (OVA) and challenged once a week with the inhalation of the same antigen over a 24 week period. Five days after the last antigen challenge, airway responsiveness to inhaled histamine was determined, the animals were then sacrificed, and the lungs and tracheae were removed. Airway responsiveness in this model was significantly increased compared with that in control animals that were challenged with saline. Pharmacological experiments using extracted tracheal and bronchial smooth muscle revealed that carbamylcholine-induced tracheal muscle contraction was significantly greater in the remodeling model than in the control animals. In the contrast, isoproterenol-induced tracheal muscle relaxation was significantly lower in the remodeling model than in the control animals. The treatment with intraperitoneal injection of 20 mg/kg or 40 mg/kg triamcinolone before each OVA challenge significantly blocked the development of airway remodeling, an increase in airway hyperresponsiveness and changes in pharmacological properties of airway smooth muscle. Thus, the present results indicate that airway remodeling enhances an airway responsiveness to nonspecific stimuli and alters contractile and relaxing responses of airway smooth muscle, and these changes can be prevented by corticosteroids together with structural changes of airways.
獨協医科大学の論文
2003-03-25

<Original Paper>Airway Remodeling in a Guinea Pig Model of Chronic Asthma : Its Influence on Airway Responsiveness and Pharmacological Properties of Airway Smooth Muscle, and Its Prevention by Corticosteroids

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