Journal of Applied Physiology, Vol 69, Issue 5 1786-1791, Copyright © 1990 by American Physiological Society
Nonadrenergic bronchodilation induced by high concentrations of sulfur dioxide
D. C. Thompson, J. L. Szarek, R. J. Altiere and L. Diamond
School of Pharmacy, University of Colorado, Boulder 80309-0297.
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.
