ROLE OF SUBSTANCE-P AND NEUROKININ-A IN TOLUENE DIISOCYANATE-INDUCED INCREASED AIRWAY RESPONSIVENESS IN RABBITS

The aim of the present study was to examine the role of neuropeptides, especially substance P (SP) and neurokinin A (NKA), in toluene diisoc yanate (TDI)-induced airway hyperresponsiveness (AHR) to acetylcholine aerosols. Thirty parts per billion of TDI in air administered over 4 hours caused a significant increase in the airway constrictive respons e to acetylcholine (AGH) aerosols in rabbits (Delta R(1): 245 +/- 30%, p < 0.005) without altering basic values of respiratory, cardiovascul ar or blood gas parameters. Inhalation of the aerosolized neuropeptide s SP and NKA resulted in a similar increase in airway responsiveness ( AR) to ACH as exposure to 30 ppb TDI. To determine whether neuropeptid es contribute to TDI-induced AHR, we studied their effects after syste mic treatment with capsaicin as well as after infusion of specific syn thetic antagonists for SP and NK2 (NKA) receptors. CAPS treatment perf ormed on 4 consecutive days as well as antagonists' infusion only mode rately (p > 0.05) decreased airway responses to AGH. CAPS application prevented the TDI-induced increase in AR to ACH in all rabbits. The in crease in airway resistance to ACH did not significantly change after TDI exposure (98 +/- 22% of the control response before TDI, p > 0.05) . Simultaneous infusion of specific synthetic SP and NK2 receptor anta gonists also abolished the TDI-induced increase in airway responses to ACH in all animals investigated (p > 0.05). The results of this study demonstrate that neuropeptides, especially the tachykinins SP and NKA , are important mediators in TDI-induced AHR in rabbits.