Induction and relief of nasal congestion in ferrets infected with influenza virus.
Susceptible ferrets intranasally infected with influenza virus consistently responded with maximal nasal secretion of virus, febrile reaction, and influx of inflammatory cells into nasal lumen on day 2 post infection (d.p.i.). Polymorphonuclear leucocytes were the earliest predominant cell, followed by monocytes/macrophages while lymphocytes were maintained as a minor population throughout the 7-day period. Nasal congestion level, continuously monitored by computer aided active anterior rhinomanometry, was reproducibly maximal at 2 d.p.i., diminished in intensity the next day and returned to the basal level within 7 d.p.i. Nasal congestion was effectively relieved by a single intranasal dose of 0.1% oxymetazoline or 0.2% phenylephrine, or a single intragastric administration of pseudoephedrine. Intranasal delivery of a single dose of 1% pyrilamine relieved nasal congestion while 0.8% ipratropium bromide and 30% cimetidine were ineffective. These results suggested that nasal congestion is regulated by alpha-adrenergic receptors in the mucosal vasculature or by H1 histamine receptor, but is unaffected by inhibitors of nasal secretion regulated by the cholinergic nervous system. The present study indicates that the infectious rhinitis ferret model provides a reproducible nasal congestion pattern that can be objectively measured by a refined active anterior rhinomanometric system. This labour intensive measurement, however, makes it difficult either to conduct a large population animal study or to use it for a rapid throughput screening of new drugs. The temporal relation between the influx of inflammatory cells into the nasal lumen and the onset of nasal congestion underlies the model's relevance to the exploration of the pathogenic mechanism(s) during viral rhinitis.
Chen
K S
KS
Procter & Gamble Pharmaceutical Research Division, Miami Valley Laboratories, Procter & Gamble Company, Cincinnati, Ohio 45253-8707, USA.
Bharaj
S S
SS
King
E C
EC
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D005334:Fever / Q000821:virology; D009980:Influenza A virus; D008365:Manometry / Q000379:methods; D014663:Nasal Decongestants / Q000627:therapeutic use*; D015508:Nasal Obstruction / Q000188:drug therapy / Q000503:physiopathology / Q000821:virology*; D009504:Neutrophils / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000150:complications*; D012220:Rhinitis / Q000150:complications / Q000821:virology*
D014663:Nasal Decongestants