Sulfur dioxide and sodium metabisulfite induce bronchoconstriction in the 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 studied the effects of sodium metabisulfite, an agent that is suggested to increase airway resistance via activation of sensory nerves. Sulfur dioxide (250 ppm) induced a characteristic biphasic bronchoconstriction. Concomitantly sulfur dioxide induced the release of calcitonin gene-related peptide (CGRP) from capsaicin-sensitive sensory nerves into the pulmonary circulation. In lungs of guinea pigs 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 sulfur dioxide, indicating that a local neural reflex depending on sodium channels was operant. Inhibition of the vanilloid receptor with capsazepine slightly, although not significantly, reduced the contractile responses to sulfur dioxide. Sodium metabisulfite, when infused via the pulmonary circulation (3 mM), induced bronchoconstriction which was abolished by capsaicin pretreatment, but not significantly reduced by capsazepine. The results indicate that in the isolated guinea pig lung inhaled sulfur dioxide induces initial bronchoconstriction in part via sensory nerve activation, while other mechanisms are involved in the late effect. Sensory nerve activation appears to be the only mechanism for bronchoconstriction induced by infused sodium metabisulfite. A role for sensory nerve-mediated bronchoconstriction by sulfur dioxide or sodium metabisulfite via activation of the vanilloid receptor could not be conclusively demonstrated by this study using capsazepine.
Bannenberg
G
G
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Atzori
L
L
Xue
J
J
Auberson
S
S
Kimland
M
M
Ryrfeldt
A
A
Lundberg
J M
JM
Moldéus
P
P
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D012121:Respiration, Artificial; D013447:Sulfites / Q000494:pharmacology*; D013458:Sulfur Dioxide / Q000494:pharmacology*
D013447:Sulfites; D013458:Sulfur Dioxide; C005200:sodium metabisulfite; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin