Kobayashi T, Shinozaki Y
Department of Basic Medical Sciences, National Institute for Environmental Studies, Ibaraki, Japan.
J Toxicol Environ Health. 1992 Nov;37(3):451-61. doi: 10.1080/15287399209531683.
In the present study, we investigated (1) whether airway responsiveness to inhaled histamine-aerosol could be induced during 7-d exposure of guinea pigs to 4 ppm NO2 and, if so, (2) whether thromboxane A2 may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n = 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO2 for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw0) did not change significantly after exposure to 4 ppm NO2 or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO2, the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl (SRaw after inhalation of 0.9% NaCl), were 1.07 +/- 0.20, 1.30 +/- 0.20, and 1.01 +/- 0.18 mM for the 3 groups later given NO2 for 1, 3, and 7 d, respectively. Following exposure to NO2 for 1, 3, or 7 d, EC200His values were 1.42 +/- 0.25, 0.66 +/- 0.10 (p < .05), and 1.05 +/- 0.22 mM, respectively. These results show that 7-d exposure to 4 ppm NO2 induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO2 than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long-term exposure, and (2) thromboxane A2 may play an important role in this transient airway hyperresponsiveness.
在本研究中，我们调查了：（1）豚鼠在7天内暴露于4 ppm二氧化氮环境下，是否会诱发对吸入组胺气雾剂的气道反应性；如果会诱发，（2）血栓素A2是否参与了这种反应性的增加。雌性Hartley豚鼠被分为6组（每组n = 15）。3组暴露于过滤空气中，另外3组分别暴露于二氧化氮环境1、3或7天（每天24小时）。暴露于4 ppm二氧化氮或空气后，基线特异性气道阻力（SRaw0）无显著变化。在暴露开始前1周和暴露结束当天测定气道反应性。在暴露于二氧化氮之前，对于之后分别暴露于二氧化氮1、3和7天的3组豚鼠，使SRawNaCl（吸入0.9%氯化钠后的SRaw）加倍所需的吸入组胺浓度（EC200His）分别为1.07±0.20、1.30±0.20和1.01±0.18 mM。暴露于二氧化氮1、3或7天后，EC200His值分别为1.42±0.25、0.66±0.10（p <.05）和1.05±0.22 mM。这些结果表明，7天暴露于4 ppm二氧化氮会在第3天诱发气道反应性显著增加。暴露于空气对气道反应性无显著影响。这种短暂的高反应性被血栓素合成酶的特异性抑制剂OKY 046所抑制。这些结果表明：（1）比先前报道浓度更低（4 ppm）的二氧化氮在适当的长期暴露期间可诱发豚鼠短暂的高反应性；（2）血栓素A2可能在这种短暂的气道高反应性中起重要作用。
