Karlsson J A, Zackrisson C, Erjefält J, Forsberg K
Department of Exploratory Pharmacology, AB Draco, Lund, Sweden.
Pulm Pharmacol. 1992 Sep;5(3):191-8. doi: 10.1016/0952-0600(92)90040-n.
The relationship between airway responsiveness to bronchoconstrictor- and cough-inducing stimuli has been examined in Ascaris suum-sensitized conscious guinea-pigs. Guinea-pigs were sensitized to Ascaris suum [4000 PNU and 100 mg Al(OH)3 i.p. on days 1 and 7] and then challenged with aerosolized antigen on days 21, 28 and 35. At day 35, antigen-exposure produced an early bronchoconstrictor response (EBR) and in about 50% of the animals also a late bronchoconstrictor response (LBR) commencing 4-8 h later. The bronchial responsiveness to inhaled histamine was increased in sensitized guinea-pigs and increased further 20-24 h after acute antigen challenge. Guinea-pigs developing only EBR were equally sensitive to histamine as those having both EBR and LBR. In contrast, the cough and reflex bronchoconstriction produced by inhaled citric acid (0.40 M, acting on capsaicin-sensitive sensory neurons) and cigarette smoke (3 min exposure; exciting both capsaicin-sensitive neurons and rapidly adapting stretch receptors) were not altered by sensitization. Furthermore, acute antigen challenge did not alter the effect of citric acid as measured 24 h later. The antigen-induced airway hyperresponsiveness to histamine was not accompanied by an altered sensitivity of airway sensory nerves mediating cough (and reflex bronchoconstriction), demonstrating that bronchial- (airway obstruction) and sensory- (cough) hyperresponsiveness involve separate and independent mechanisms.
在猪蛔虫致敏的清醒豚鼠中,已对气道对支气管收缩剂和诱发咳嗽刺激的反应性之间的关系进行了研究。豚鼠对猪蛔虫致敏(第1天和第7天腹腔注射4000个猪蛔虫蛋白氮单位和100毫克氢氧化铝),然后在第21天、28天和35天用雾化抗原进行激发。在第35天,抗原暴露产生了早期支气管收缩反应(EBR),并且在大约50%的动物中还产生了4-8小时后开始的晚期支气管收缩反应(LBR)。致敏豚鼠对吸入组胺的支气管反应性增加,在急性抗原激发后20-24小时进一步增加。仅出现EBR的豚鼠对组胺的敏感性与同时出现EBR和LBR的豚鼠相同。相比之下,吸入柠檬酸(0.40 M,作用于辣椒素敏感感觉神经元)和香烟烟雾(暴露3分钟;刺激辣椒素敏感神经元和快速适应的牵张感受器)所产生的咳嗽和反射性支气管收缩并未因致敏而改变。此外,急性抗原激发在24小时后测量时并未改变柠檬酸的作用。抗原诱导的气道对组胺的高反应性并未伴随着介导咳嗽(和反射性支气管收缩)的气道感觉神经敏感性的改变,这表明支气管(气道阻塞)和感觉(咳嗽)高反应性涉及不同且独立的机制。