Am. J. Respir. Crit. Care Med., Volume 157, Number 5, May 1998, 1506-1511

Human Respiratory Syncytial Virus Produces Prolonged Alterations of Neural Control in Airways of Developing Ferrets

GIUSEPPE N. COLASURDO, VAL G. HEMMING, GREGORY A. PRINCE, ANDREW S. GELFAND, JOAN E. LOADER, and GARY L. LARSEN

Division of Pediatric Pulmonary Medicine, National Jewish Medical and Research Center, University of Colorado School of Medicine, Denver, Colorado; Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda; and Virion Systems, Inc., Rockville, Maryland

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 () 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.

This article has been cited by other articles:

				E. M. Bozanich, R. A. Collins, C. Thamrin, Z. Hantos, P. D. Sly, and D. J. Turner Developmental changes in airway and tissue mechanics in mice J Appl Physiol, July 1, 2005; 99(1): 108 - 113. [Abstract] [Full Text] [PDF]

				A. Auais, B. Adkins, G. Napchan, and G. Piedimonte Immunomodulatory effects of sensory nerves during respiratory syncytial virus infection in rats Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L105 - L113. [Abstract] [Full Text] [PDF]

				A. M. Khan, O. Elidemir, C. E. Epstein, K. P. Lally, H. Xue, M. Blackburn, G. L. Larsen, and G. N. Colasurdo Meconium aspiration produces airway hyperresponsiveness and eosinophilic inflammation in a murine model Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L785 - L790. [Abstract] [Full Text] [PDF]

				M. Y. Khassawneh, I. A. Dreshaj, S. Liu, C.-H. Chang, M. A. Haxhiu, and R. J. Martin Endogenous nitric oxide modulates responses of tissue and airway resistance to vagal stimulation in piglets J Appl Physiol, August 1, 2002; 93(2): 450 - 456. [Abstract] [Full Text] [PDF]

				Z.-X. Wu, D. F. Maize Jr., B. E. Satterfield, D. G. Frazer, J. S. Fedan, and R. D. Dey Role of intrinsic airway neurons in ozone-induced airway hyperresponsiveness in ferret trachea J Appl Physiol, July 1, 2001; 91(1): 371 - 378. [Abstract] [Full Text] [PDF]

				K. A. King, C. Hu, M. M. Rodriguez, R. Romaguera, X. Jiang, and G. Piedimonte Exaggerated Neurogenic Inflammation and Substance P Receptor Upregulation in RSV-Infected Weanling Rats Am. J. Respir. Cell Mol. Biol., February 1, 2001; 24(2): 101 - 107. [Abstract] [Full Text]

				Y. J. KAO, P. A. PIEDRA, G. L. LARSEN, and G. N. COLASURDO Induction and Regulation of Nitric Oxide Synthase in Airway Epithelial Cells by Respiratory Syncytial Virus Am. J. Respir. Crit. Care Med., February 1, 2001; 163(2): 532 - 539. [Abstract] [Full Text]

				W. Zhu and R. D. Dey Projections and Pathways of VIP- and nNos-Containing Airway Neurons in Ferret Trachea Am. J. Respir. Cell Mol. Biol., January 1, 2001; 24(1): 38 - 43. [Abstract] [Full Text]

				O. ELIDEMIR, L. L. FAN, and G. N. COLASURDO A Novel Diagnostic Method for Pulmonary Aspiration in a Murine Model . Immunocytochemical Staining of Milk Proteins in Alveolar Macrophages Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 622 - 626. [Abstract] [Full Text]