Modulation of sulfur dioxide-induced airways hyperresponsiveness in the conscious dog

Brief exposure of conscious dogs to 30 ppm SO2 directly into the lungs resulted in a transient bronchoconstriction followed by a period of hypersensitivity to aerosolized methacholine and 5-hydroxytryptamine. The hypersensitivity was maximal 4 h after exposure to SO2. Both Wy-41,195 and disodium cromoglycate, two antiallergic drugs, inhibited the hypersensitivity to methacholine when administered just prior to methacholine challenge. Neither drug significantly influenced SO2-induced bronchospasm nor influenced methacholine hypersensitivity when administered just prior to SO2 exposure. Furthermore, Wy-41,195 was ineffective against methacholine hypersensitivity when administered orally for 4 days. SO2-induced airway hypersensitivity in the dog may thus provide a useful model for exploring mechanisms and pharmacologic modulation of bronchial hyperreactivity, a common feature of asthma.