Sorkness R, Clough J J, Castleman W L, Lemanske R F
Department of Medicine, University of Wisconsin, Madison.
Am J Respir Crit Care Med. 1994 Jul;150(1):28-34. doi: 10.1164/ajrccm.150.1.8025764.
Viral respiratory infections in humans have been associated with exacerbations of late allergic responses and asthma, as well as with airway abnormalities that persist after resolution of the acute infection. We hypothesized that augmented parasympathetic contractile mechanisms may contribute to postviral airway dysfunction. We studied airway physiology in anesthetized rats at 1 to 8 wk after inoculation with Parainfluenza 1 virus or vehicle. The virus groups had airway obstruction (abnormal lung mechanics, gas exchange and residual volume), and increased sensitivity to intravenous methacholine at 1 to 4 wk, although methacholine hypersensitivity was minimal in vagotomized rats; these abnormalities were absent at 7 to 8 wk after inoculation. Airway responses to vagal parasympathetic nerve stimulation were enhanced markedly at 1 to 4 wk, and significantly at 7 to 8 wk, after viral inoculation. Dysfunction of M2 muscarinic autoreceptors during acute viral infection was indicated by a significant attenuation of gallamine-induced augmentation of airway parasympathetic responses; in contrast, gallamine-augmentation of parasympathetic responses at 2 to 8 wk after viral inoculation was not different from noninfected control animals. We conclude that respiratory virus infection in rats produces airway dysfunction that remains for weeks after resolution of the acute infection, and that is caused in part by parasympathetic hyperresponsiveness, associated both with M2 autoreceptor malfunction and with M2-independent mechanism(s).
人类的病毒性呼吸道感染与迟发性过敏反应和哮喘的加重有关，也与急性感染消退后持续存在的气道异常有关。我们推测，副交感神经收缩机制增强可能导致病毒感染后的气道功能障碍。我们研究了接种1型副流感病毒或赋形剂后1至8周麻醉大鼠的气道生理学。病毒感染组在1至4周时出现气道阻塞（异常的肺力学、气体交换和残气量），对静脉注射乙酰甲胆碱的敏感性增加，尽管在迷走神经切断的大鼠中乙酰甲胆碱超敏反应最小；接种后7至8周这些异常消失。病毒接种后1至4周，气道对迷走神经副交感神经刺激的反应明显增强，7至8周时显著增强。急性病毒感染期间M2毒蕈碱自受体功能障碍表现为加拉明诱导的气道副交感反应增强显著减弱；相比之下，病毒接种后2至8周加拉明诱导的副交感反应增强与未感染的对照动物无差异。我们得出结论，大鼠呼吸道病毒感染会导致气道功能障碍，在急性感染消退后持续数周，部分原因是副交感神经反应过度，这与M2自受体功能障碍和M2非依赖性机制有关。
