SULFUR-DIOXIDE AND SODIUM METABISULFITE INDUCE BRONCHOCONSTRICTION INTHE ISOLATED-PERFUSED AND VENTILATED GUINEA-PIG LUNG VIA STIMULATION OF CAPSAICIN-SENSITIVE SENSORY NERVES

In this study the relationship between sulfur dioxide-induced sensory nerve activation and acute bronchoconstriction was assessed. We also s tudied the effects of sodium metabisulfite, an agent that is suggested to increase airway resistance via activation of sensory nerves. Sulfu r dioxide (250 ppm) induced a characteristic biphasic bronchoconstrict ion. Concomitantly sulfur dioxide induced the release of calcitonin ge ne-related peptide (CGRP) from capsaicin-sensitive sensory nerves into the pulmonary circulation. In lungs of guinea pi,os pretreated with a neurotoxic dose of capsaicin, the first phase of bronchoconstriction was reduced and the overflow of CGRP was not detectable. Tetrodotoxin abolished the initial phase of the bronchoconstriction induced by sulf ur dioxide, indicating that a local neural reflex depending on sodium channels was operant. Inhibition of the vanilloid receptor with capsaz epine slightly, although not significantly, reduced the contractile re sponses to sulfur dioxide. Sodium metabisulfite, when infused via the pulmonary circulation (3 mM), induced bronchoconstriction which was ab olished by capsaicin pretreatment, but not significantly reduced by ca psazepine. The results indicate that in the isolated guinea pig lung i nhaled sulfur dioxide induces initial bronchoconstriction in part via sensory nerve activation, while other mechanisms are involved in the l ate effect. Sensory nerve activation appears to be the only mechanism for bronchoconstriction induced by infused sodium metabisulfite. A rol e for sensory nerve-mediated bronchoconstriction by sulfur dioxide or sodium metabisulfite via activation of the vanilloid receptor could no t be conclusively demonstrated by this study using capsazepine.