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 effe cts 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 ex posed to 0.8 ppm ozone or air for 2 hr. In some lungs (9 or 10 each gr oup), increasing doses of methacholine followed by capsaicin were inje cted into the pulmonary artery. In separate lungs (n = 5, each group), lung Substance P content by EIA and NK1 receptor characteristics by r adioligand binding were measured. Analyses were performed by two-way A NOVA with a significant interaction indicative of C-fibers playing a r ole in ozone responses. Ozone increased R(L) and decreased C-dyn, effe cts which were apparently not dependent on C-fibers. Ozone increased r esponsiveness to methacholine, an effect which was reduced by depletio n of C-fibers. Ozone increased and C-fiber depletion decreased lung re sponses to capsaicin. C-fiber depletion but not ozone decreased lung s ubstance P content. C-fiber depletion increased the affinity but did n ot change the number of NK, receptors, while ozone had no effect. We c onclude that the ozone, in the absence of systemic effects and the blo od components of inflammation, increased muscarinic reactivity in part via the local effects of C-fibers. (C) 1996 Academic Press, Inc.