In vivo and in vitro studies on the use of the guinea pig as a model for virus-provoked airway hyperreactivity.
The parainfluenza 3 (P-3)-infected guinea pig was examined as a model for virus-provoked airway hyperreactivity by measuring changes in airway overflow pressure in response to intravenously (iv) administered histamine. In vitro responses of lung parenchymal strips to several contractile substances were also measured. All studies were conducted 4 days after nasal insufflation with P-3 or P-3 growth medium (control). Increases in airway overflow pressure caused by histamine were enhanced by P-3 infection, and the dose required to produce a standard level of response was decreased (i.e., there was an increase in sensitivity to histamine). Enhancement of in vivo histamine responses caused by P-3 was prevented both by cutting the vagus nerves in the midcervical region and by iv administered hexamethonium, 5 mg/kg. The enhancement was not blocked by 1 mg/kg of atropine given iv, but was blocked by a larger dose 5 mg/kg. The larger dose of atropine significantly antagonized responses to histamine in the P-3-infected state. Increases in airway overflow pressure produced by electrical stimulation of the left vagus and nicotine (1 and 10 mg/kg given iv), both studied after bilateral vagotomy and propranolol, 1 mg/kg given iv, were also enhanced by P-3 infection. Atropine, 1 mg/kg given iv blocked the P-3-induced enhancement of responses to vagus stimulation. Propranolol, 1 mg/kg, and phentolamine, 3 mg/kg, given together iv, produced a doubling of the airway overflow pressure only in P-3-infected animals. Propranolol alone or other receptor antagonists did not produce as marked a change in either group of animals.(ABSTRACT TRUNCATED AT 250 WORDS)