Human Respiratory Syncytial Virus Produces Prolonged Alterations of Neural Control in Airways of Developing Ferrets
- 1 May 1998
- journal article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 157 (5), 1506-1511
- https://doi.org/10.1164/ajrccm.157.5.9705026
Abstract
A dysfunction of pathways that normally cause contraction or relaxation of airways has been proposed to explain heightened levels of responsiveness produced by various insults to the airway. For example, we previously reported (4) that infection of cotton rats with the human respiratory syncytial virus (HRSV) leads to a significant decrease in an airway's nonadrenergic noncholinergic inhibitory (NANCi) response shortly after the infection. In the present study we addressed the more chronic effects of HRSV infection on airway function in young ferrets during a period of rapid somatic growth. Animals 1 wk old received HRSV or uninfected cell culture medium intranasally. In vitro studies of airway function were performed on tracheal smooth muscle (TSM) segments at 4, 8, and 24 wk of age. To evaluate neurally mediated contractile responses, frequency-response curves to electrical field stimulation (EFS) were performed with results expressed in terms of the frequency causing 50% of the maximal contractile response (ES50). In addition, contractile responses of TSM to methacholine (MCh) were also assessed with results expressed as the concentration needed to produce 50% of the maximal contractile response (EC50). To gauge NANCi responses, TSM was contracted with neurokinin A in the presence of atropine, propranolol, and indomethacin. Relaxant responses to EFS were assessed at frequencies from 5 to 30 Hz, with results expressed as mean percent relaxation. We found increased contractile responses to EFS in infected animals compared with that in the control group in both 4- and 8-wk old animals (p = 0.001 and p = 0.008, respectively). This difference had resolved by 24 wk of age. There was no difference in TSM responses to MCh between the groups at any age. Although there were no NANCi responses in 4-wk-old ferrets from either group, NANCi responses were significantly decreased in 8-wk-old ferrets previously infected with HRSV in the first week of life (p = 0.0001). A significant difference persisted (p = 0.008), albeit to a lesser degree, at 24 wk of age. These findings demonstrate that HRSV produces prolonged alterations of TSM function in ferret airways in vitro.Keywords
This publication has 20 references indexed in Scilit:
- Viral infection induces dependence of neuronal M2 muscarinic receptors on cyclooxygenase in guinea pig lung.JCI Insight, 1996
- Decrease in the airways' nonadrenergic noncholinergic inhibitory system in allergen sensitized rabbitsPediatric Pulmonology, 1994
- Respiratory syncytial virus puzzle: Clinical features, pathophysiology, treatment, and preventionThe Journal of Pediatrics, 1992
- The bronchial epithelium as a target for inflammatory attack in asthmaClinical and Experimental Allergy, 1992
- Parainfluenza virus infection damages inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves in the guinea‐pigBritish Journal of Pharmacology, 1991
- Clues to the Mechanisms of Virus-Induced Asthma from Animal ModelsSeminars in Respiratory and Critical Care Medicine, 1990
- Rhinovirus upper respiratory infection increases airway hyperreactivity and late asthmatic reactions.JCI Insight, 1989
- Respiratory infections and bronchial hyperreactivityJournal of Allergy and Clinical Immunology, 1988
- Muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pigBritish Journal of Pharmacology, 1984
- Adrenergic and non-adrenergic inhibitory nerves in mammalian airwaysJournal of the Autonomic Nervous System, 1982