IS THERE LOSS OF A PROTECTIVE MUSCARINIC RECEPTOR MECHANISM IN ASTHMA
IS THERE LOSS OF A PROTECTIVE MUSCARINIC RECEPTOR MECHANISM IN ASTHMA
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DOI：
10.1378/chest.96.6.1285
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发表时间：
1989-12-01
期刊：
影响因子：
9.6
通讯作者：
AHMED, T
中科院分区：
文献类型：
--
作者：
AYALA, LE;AHMED, T
我们研究了先前气道毒蕈碱受体刺激（雾化甲胆碱）会改变支气管收缩器对组胺的反应的假设，这部分是迷走神经介导的。在4个不同的实验日，对15名受试者（9名正常受试者和6名哮喘受试者）随机进行如下甲胆碱和组胺吸入挑战：甲胆碱-组胺，组胺-甲胆碱；甲基苯丙胺和组胺。估计导致SGaw下降50%的每种激动剂的累积激发剂量（PD50）。第二次挑战在第一次挑战后大约1小时进行，当SGaw恢复到基线时。在正常受试者中，先前用甲胆碱刺激毒蕈碱可抑制随后对组胺的支气管收缩反应（平均+-）。SE PD50组胺从13.7 +-升高。3.1至28.4 .+-。7.2呼吸单位)，不改变支气管缩窄剂对甲胆碱的反应。在哮喘受试者中，先前的甲胆碱暴露不能改变支气管收缩对组胺和甲胆碱的反应。相比之下，在正常和哮喘受试者中，先前使用组胺并没有改变随后对组胺和甲胆碱的支气管收缩反应。异丙托溴铵预处理可减轻组胺诱导的支气管收缩，提示组胺的气道作用部分是迷走神经介导的。这些数据表明，先前的毒蕈碱刺激对正常受试者组胺诱导的支气管收缩具有保护作用，哮喘患者缺乏这种抑制作用可能表明毒蕈碱受体保护性机制的丧失。
We investigated the hypothesis that prior airway muscarinic receptor stimulation (with aerosolized methacholine) would modify the bronchoconstrictor response to histamine, which is, in part, vagally mediated. On four different experiment days, the following combinations of methacholine and histamine inhalation challenges were performed in 15 subjects (nine normal and six asthmatic) in a random fashion: methacholine-histamine, histamine-methacholine; methacholine-methacholine and histamine-histamine. Cumulative provocative dose of each agonist which caused a 50 percent decrease in SGaw was estimated (PD50). The second challenge was performed approximately 1 hour after the first challenge, when SGaw had returned to baseline. In normal subjects, prior muscarinic stimulation with methacholine suppressed the subsequent bronchoconstrictor response to histamine (mean .+-. SE PD50 histamine increased from 13.7 .+-. 3.1 to 28.4 .+-. 7.2 breath units), without modifying the bronchoconstrictor response to methacholine. In asthmatic subjects, prior methacholine exposure failed to modify the bronchoconstrictor responses to histamine and methacholine. In contrast, prior challenge with histamine did not modify the subsequent bronchoconstrictor responses to histamine and methacholine in both normal and asthmatic subjects. Pretreatment with ipratropium bromide attenuated the histamine-induced bronchoconstriction, suggesting that airway effects of histamine, in part, are vagally mediated. These data suggest that prior muscarinic stimulation has a protective effect on histamine-induced bronchoconstriction in normal subjects and the absence of this inhibitory effect in asthmatic patients may represent loss of a protective muscarinic receptor mechanism.