The local C-fiber contribution to ozone-induced effects on the isolated guinea pig lung

We studied the local role of C-fibers, in the absence of systemic effects and blood components of inflammation, on lung responses to ozone. Guinea pigs were pretreated with capsaicin to deplete C-fibers or with vehicle. One week later their isolated, buffer-perfused lungs were exposed to 0.8 ppm ozone or air for 2 hr. In some lungs (9 or 10 each group), increasing doses of methacholine followed by capsaicin were injected into the pulmonary artery. In separate lungs (n = 5, each group), lung Substance P content by EIA and NK1 receptor characteristics by radioligand binding were measured. Analyses were performed by two-way ANOVA with a significant interaction indicative of C-fibers playing a role in ozone responses. Ozone increased R(L) and decreased C(dyn), effects which were apparently not dependent on C-fibers. Ozone increased responsiveness to methacholine, an effect which was reduced by depletion of C-fibers. Ozone increased and C-fiber depletion decreased lung responses to capsaicin. C-fiber depletion but not ozone decreased lung substance P content. C-fiber depletion increased the affinity but did not change the number of NK1 receptors, while ozone had no effect. We conclude that the ozone, in the absence of systemic effects and the blood components of inflammation, increased muscarinic reactivity in part via the local effects of C-fibers.