Hyperreactive airway smooth muscle responsiveness after inhalation of toluene diisocyanate vapors

Guinea pigs were exposed to 29 parts per billion of toluene diisocyanate (TDI) vapors 5 h per day for 20 consecutive days. Control animal exposure was to filtered air, with similar length of exposure, air flow, heat load, humidity, and other factors. Animals were killed 20 h after the last exposure, and tracheal smooth muscle relaxation and contraction responses to agonists were determined. There was no difference in beta-adrenergic responsiveness between the 2 groups; the mean -log ED50 (concentration of agonist corresponding to 50% of maximal effect) for isoproterenol-induced responses was similar (9.73 +/- 0.06 SE for exposed animals and 9.56 +/- 0.13 for control animals, p = 0.29). Significant differences in carbachol-produced contractility were observed. The dose-effect curve from carbachol-stimulated strips was shifted upward and to the left for TDI-exposed animals. Beginning with the lowest dose of carbachol, significant differences were observed between exposure groups; these differences became even more pronounced as the concentration of carbachol was increased. The mean -log ED50 of carbachol-treated strips from TDI-exposed animals was 6.44 + 0.04 SE, which was significantly lower than that of the control strips, 6.23 + 0.04 (p = 0.01). The maximal smooth muscle tension was also greater in TDI-exposed animals. The observed increase in maximal tension and the shift of the dose-effect curve for TDI-exposed animals suggest a direct effect of TDI on tracheal smooth muscle.