The objective of the present experiments was to study the effects of
pulmonary inflammation induced by subacute
Sulfur-dioxide (SO(2)) exposure on
capsaicin-induced responses in isolated primary vagal sensory neurons and
cough. Additionally, we examined the effects of SO(2) exposure on respiratory function and lung histology. All experiments were conducted 24 h after 4 days of subacute SO(2) (1000 ppm, 3 h/day for 4 days) exposure. In in vitro experiments, intracellular Ca(2+) concentrations were measured in single nodose ganglia cells isolated from SO(2) treated and control guinea pigs, using a fluorescence-based methodology. In nodose ganglia cells from SO(2)-exposed animals, intracellular Ca(2+) responses evoked by
capsaicin (1 x 10(-7) and 1 x 10(-6) M) were significantly augmented (87% and 59%, respectively) compared to nodose ganglia from control animals. In vivo experiments,
cough responses induced by a submaximal dose of aerosolized
capsaicin (30 microM) were increased approximately 50% in SO(2) exposed animals compared to control animals. The enhanced
cough response produced by SO(2) was inhibited by the
corticosteroid,
dexamethasone (10 mg/kg, p.o. b.i.d for 4 days and 10 mg/kg, p.o. once on day 5). In separate experiments, guinea pigs exposed to SO(2) displayed a decrease in respiratory frequency and minute ventilation and an increase in enhanced pause (PenH), a surrogate measure for pulmonary obstruction. Associated with the SO(2)-induced increase in
cough and changes in respiratory parameters was an increase in BAL neutrophils. BAL neutrophil counts were 5+/-4 and 691+/-141 cells x 10(3)/ml for air and SO(2)-exposed animals, respectively. The neutrophillic
inflammation induced by SO(2) was attenuated by
dexamethasone treatment. Finally, staining for
collagen, smooth muscle and goblet cells showed
inflammation, remodeling and goblet cell metaphasia in the SO(2)-exposed animals. Our results demonstrate that SO(2) exposure enhances
TRPV1 receptor function at the level of the nodose ganglia. This effect occurs in parallel with an increase sensitivity of the
cough response to
capsaicin.