Increase in Respiratory Resistance After Exercise in Conscious Guinea Pigs. as a Model for Exercise-Induced Asthma

Abstract

We have developed an experimental model for exercise-induced asthma (EIA) using conscious guinea pigs. Respiratory resistance (Rrs) was measured before and after exercise (running). When a 0.05% lipopolysaccharide (LPS) was inhaled by guinea pigs which had been pretreated with a corticosteroid biosynthesis inhibitor metyrapone (50 mg/kg, i. v.), Rrs significantly increased 24 h after exercise. Metyrapone had no effect, however, on the LPS-induced increase in the numbers of macrophages, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF). In order to examine the role of airway inflammation, the effects of murine recombinant interleukin-5 (mrIL-5) and platelet activating factor (PAF) were investigated in guinea pigs. The exercise-elicited increase in Rrs was observed 24 h later than the treatment with mrIL-5 in metyrapone-treated animals. The number of macrophages, eosinophils and neutrophils increased in the BALF of mrIL-5-treated animals. In contrast, a 0.05% PAF aerosol caused an increased number of eosinophils in BALF, but did not affect Rrs after exercise in either metyrapone-treated or non-treated animals. Moreover, to evaluate the value of this model as a pharmacological tool, the effect of ketotifen and prednisolone on the exercise-induced increase in Rrs was investigated. Prior administration of ketotifen and prednisolone showed a tendency to prevent, or clearly inhibited, the exercise-induced increase in Rrs in animals treated with the combination with LPS and metopyrone. © 1995, The Pharmaceutical Society of Japan. All rights reserved.