Sulfur dioxide-induced bronchoconstriction via ruthenium red-sensitive activation of sensory nerves.
The mechanism of sulfur dioxide-induced bronchoconstriction was studied using isolated perfused and ventilated guinea-pig lungs. They were exposed to sulfur dioxide after pretreatment with different compounds, either via the pulmonary artery or via the air passages. Neither the cyclooxygenase inhibitor indomethacin (30 microM) nor the H1-receptor antagonist diphenhydramine (15 microM), given via the perfusate, attenuated the sulfur dioxide-induced bronchoconstriction. Furthermore, sulfur dioxide exposure did not cause a release of either thromboxane or histamine into the perfusate. In experiments with atropine equivocal results were obtained with regard to protection against sulfur dioxide-evoked bronchoconstriction. Intratracheal instillation of the local anesthetic agent lidocaine (1 mg/50 microliters) markedly reduced the sulfur dioxide-induced bronchoconstriction. Also, ruthenium red (10 microM), an agent with calcium entry-blocking properties and an inhibitor of capsaicin-induced bronchoconstriction, was able to inhibit the effect of sulfur dioxide. The sulfur dioxide-induced bronchoconstriction was associated with release of calcitonin gene-related peptide, a sensory neuropeptide. The effect of sulfur dioxide was also inhibited by a Ca(2+)-free buffer plus EGTA. These results suggest that sulfur dioxide-induced bronchoconstriction in the guinea-pig lung is the result of a local effect on sensory nerves (C-fiber activation). The mechanism seems to be dependent on the Ca(2+)-dependent release of sensory neuropeptides and to be linked to opening of the cation channel, which is associated with the proposed capsaicin receptor on sensory nerves as revealed by the inhibitory effect of ruthenium red.
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D012430:Ruthenium Red / Q000494:pharmacology*; D011984:Sensory Receptor Cells / Q000187:drug effects; D013458:Sulfur Dioxide / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism
D013458:Sulfur Dioxide; D012430:Ruthenium Red; D013928:Thromboxane A2; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide