NEUROPEPTIDES MEDIATE THE OZONE-INDUCED INCREASE IN THE PERMEABILITY OF THE TRACHEAL MUCOSA IN GUINEA-PIGS

We examined the effects of acute exposure to ozone on the permeability of the tracheal mucosa and the contribution of neural pathways to the effects of ozone using horseradish peroxidase (HRP; mol wt 40,000) as a marker of lumen-to-blood transfer of a macromolecule in guinea pigs in vivo. Each guinea pig was anesthetized and exposed for 30 min to e ither ozone [0.5 or 3 parts/million (ppm)] or air. Immediately after e xposure, a tracheal segment was isolated between two polyethylene cann ulas in vivo and filled with HRP solution (50 mg/ml). Blood samples we re drawn before and 10, 20, 30, and 40 min after the intratracheal ins tillation of HRP. The plasma levels of HRP in guinea pigs exposed for 30 min to 3 ppm of ozone, but not to 0.5 ppm of ozone, were significan tly greater than those in guinea pigs exposed to air. Although the inc reased plasma HRP levels after exposure to 3 ppm of ozone were unaffec ted by propranolol or atropine, they were completely inhibited by pret reatment with capsaicin (50 mg/kg sc, injected in two doses). These re sults suggest that endogenous neuropeptides mediate the ozone-induced increase in the permeability of the tracheal mucosa in guinea pigs in vivo, but neither an adrenergic nor a cholinergic pathway appears to b e involved.