VIRUS-INDUCED AIRWAY-OBSTRUCTION AND PARASYMPATHETIC HYPERRESPONSIVENESS IN ADULT-RATS

Viral respiratory infections in humans have been associated with exace rbations of late allergic responses and asthma, as well as with airway abnormalities that persist after resolution of the acute infection. W e hypothesized that augmented parasympathetic contractile mechanisms m ay contribute to postviral airway dysfunction. We studied airway physi ology in anesthetized rats at 1 to 8 wk after inoculation with Parainf luenza 1 virus or vehicle. The virus groups had airway obstruction (ab normal lung mechanics, gas exchange, and residual volume), and increas ed sensitivity to intravenous methacholine at 1 to 4 wk, although meth acholine hypersensitivity was minimal in vagotomized rats; these abnor malities 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. Dys function of M(2) muscarinic autoreceptors during acute viral infection was indicated by a significant attenuation of gallamine-induced augme ntation of airway parasympathetic responses; in contrast, gallamine-au gmentation of parasympathetic responses at 2 to 8 wk after viral inocu lation 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 th at is caused in part by parasympathetic hyperresponsiveness, associate d both with M(2) autoreceptor malfunction and with M(2)-independent me chanism(s).