Nonadrenergic bronchodilation induced by high concentrations of sulfur dioxide.
SO2 is an environmental pollutant known to elicit bronchospasm in susceptible subjects. We observed that brief exposure of artificially bronchoconstricted cats to high concentrations of SO2 induces a bronchodilator response. This study assessed the characteristics of this response and examined various mechanisms that might underlie it. Cats were anesthetized with diallylbarbital-urethan, and airway smooth muscle tone, measured by lung resistance and dynamic lung compliance, was elevated with a continuous infusion of 5-hydroxytryptamine. Administration of 10 breaths of SO2 via a tracheostomy induced concentration-dependent bronchodilation in the range 100-1,000 parts/million. Only infrequently was bronchoconstriction observed before bronchodilation. SO2-induced bronchodilator responses were unaffected by pretreatment with intravenous atropine or propranolol, establishing them as nonadrenergic noncholinergic (NANC) in origin. Neither the ganglionic blocking agent hexamethonium nor the nerve toxin tetrodotoxin influenced the SO2-induced bronchodilation, thus excluding a role for central or local autonomic reflexes in the response. Efforts to modulate the response by pretreatment with the cyclooxygenase inhibitor indomethacin or the mediator release inhibitor cromolyn sodium also were unsuccessful. Administration of acidic aerosols failed to mimic the SO2-induced bronchodilator response. Although the mechanism whereby SO2 induces bronchodilation under these experimental conditions remains unclear, release of a NANC inhibitory transmitter from a neural, epithelial, or other cellular source via a mechanism insensitive to both tetrodotoxin and cromolyn is a distinct possibility. An intrinsic NANC inhibitory system may exist in feline airways functioning as a local regulator of bronchomotor tone and possibly serving to override responses to strong, potentially asphyxial bronchoconstrictive stimuli.
Thompson
D C
DC
School of Pharmacy, University of Colorado, Boulder 80309-0297.
Szarek
J L
JL
Altiere
R J
RJ
Diamond
L
L
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D008170:Lung Compliance; D008297:Male; D009994:Osmolar Concentration; D013458:Sulfur Dioxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001993:Bronchodilator Agents; D013458:Sulfur Dioxide