Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs.

To determine the mechanism responsible for nitrogen dioxide (NO2)-induced airway hyperresponsiveness, we examined the effects of NO2 exposure on the contractile response to histamine and the level of histamine N-methyltransferase (HMT) activity, a histamine-degrading enzyme, in guinea pig trachea in vitro. Guinea pigs were divided into seven groups. Each group received continuous NO2 exposure (2.0 ppm) for either 2, 6, 12, 24, 48, or 96 h. The remaining group did not receive NO2 exposure (control). HMT activity in trachea was decreased from the control value of 70.3 +/- 7.7 pmol/min/mg protein to 34.6 +/- 6.7 pmol/min/mg protein by 12 h exposures of NO2. However, 24 and 48 h exposures of NO2 did not significantly alter HMT activity. In contrast, HMT activity exceeded the control value by 96 h exposures of NO2 (85.5 +/- 5.1 pmol/min/mg protein). Twelve hour exposures of NO2 shifted the concentration-response curves to histamine to lower concentrations and significantly reduced the median effective concentr...