IMPAIRED SENSORINEURAL FUNCTION AFTER ALLERGEN-INDUCED MEDIATOR RELEASE

We tested the hypothesis that allergen-induced mediator release augmen ts the magnitude of isocapnic dry gas hyperpnea-induced bronchoconstri ction in sensitized guinea pigs. Male Hartley guinea pigs were sensiti zed by spontaneous inhalation of ovalbumin (OA) aerosol on days 0 and 7 of the study. On day 14, sensitized animals again breathed OA aeroso l and were prospectively divided into a group that exhibited labored b reathing (LB), presumably reflecting OA-induced inflammatory mediator release, and a group that did not exhibit LB at this time. Control gui nea pigs breathed saline aerosol on days 0, 7, and 14. Bronchoalveolar lavage on day 17 disclosed relative eosinophilia in OA+LB, but not in OA-LB, animals. On day 17, the bronchoconstrictor responses to increa sing intravenous (iv.) doses of acetylcholine (ACh), substance P (SP), neurokinin A(NKA), and capsaicin, as well as dry gas hyperpnea, were measured in vivo in animals from each group. Control and OA-LB guinea pigs exhibited similar responses, but OA+LB animals demonstrated augme nted bronchoconstriction induced by iv. administration of ACh, SP, or NKA. However, despite their augmented responsiveness to these exogenou s constrictor agonists, OA+LB animals displayed no greater bronchocons triction after dry gas hyperpnea or iv. capsaicin administration. It i s known that both dry gas hyperpnea and iv. capsaicin cause bronchocon striction in guinea pigs by releasing endogenous tachykinins from airw ay sensory C-fibers. Thus, our results suggest that allergen-induced m ediator release impairs endogenous tachykinin release from airway sens ory C-fibers in guinea pigs.