Virus-induced airway obstruction and parasympathetic hyperresponsiveness in adult rats.
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).
Department of Medicine, University of Wisconsin, Madison.
R
R
Sorkness
J J
JJ
Clough
W L
WL
Castleman
R F
RF
Lemanske
D000818:Animals; D001249:Asthma / Q000150:complications / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D004558:Electric Stimulation; D005703:Gallamine Triethiodide / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride; D018727:Muscarinic Antagonists; D010222:Parainfluenza Virus 1, Human; D018184:Paramyxoviridae Infections / Q000150:complications*; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology; D015656:Respiratory Mechanics; D012141:Respiratory Tract Infections / Q000150:complications*; D014630:Vagus Nerve / Q000502:physiology
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D005703:Gallamine Triethiodide