Neural control mechanisms within airways: disruption by respiratory syncytial virus.
Among the factors influencing airway function are neural control mechanisms, including adrenergic, cholinergic, nonadrenergic noncholinergic inhibitory, and nonadrenergic noncholinergic excitatory pathways. Respiratory infections affect these pathways in ways that are not entirely clear.


OBJECTIVE
To determine acute and chronic effects of respiratory syncytial virus infection on airway neural control mechanisms.


METHODS
Acute effects were studied in cotton rats, which received human respiratory syncytial virus or uninfected cell culture medium intranasally at 5 weeks of age. Chronic effects were studied in ferrets, which received human respiratory syncytial virus or uninfected cell culture medium intranasally during the first 10 days of life. The responsiveness of tracheal smooth muscle segments was studied in vitro 4 days after infection of cotton rats and when ferrets were 4, 8, and 24 weeks of age.


RESULTS
Tracheal smooth muscle segments from cotton rats demonstrated significant increases in contractile responses to nerve stimulation (cholinergic responses). In the presence of neurokinin A, contractile responses increased (enhanced nonadrenergic noncholinergic excitatory response), and relaxation of airways by nerve stimulation (nonadrenergic noncholinergic inhibitory response) was severely impaired. Airway epithelium was also disrupted. These alterations favor airway obstruction and a hyper-responsive state. Contractile responses to nerve stimulation were increased in 4- and 8-week-old ferrets infected with human respiratory syncytial virus compared with ferrets in a control group, a difference that resolved by 24 weeks. Nonadrenergic noncholinergic inhibitory responses were absent in all 4-week-old ferrets and significantly decreased in 8-week-old ferrets infected with human respiratory syncytial virus. A significant difference persisted at 24 weeks of age.


CONCLUSIONS
Human respiratory syncytial virus causes acute and chronic changes in neural control of airways in animal models. When infection occurs early in life, the alterations persist for long periods.
Larsen
G L
GL
Divison of Pediatric Pulmonary Medicine, National Jewish Medical Research Center, University of Colorado School of Medicine, Denver 80206, USA.
Colasurdo
G N
GN
D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005289:Ferrets; D006801:Humans; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology / Q000821:virology; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology / Q000503:physiopathology*; D016205:Sigmodontinae; D014132:Trachea / Q000503:physiopathology* / Q000821:virology*