AIRWAY RESPONSIVENESS TO ACETYLCHOLINE IN CONGENITALLY BRONCHIAL-HYPERSENSITIVE (BHS) AND BRONCHIAL-HYPOSENSITIVE (BHR) GUINEA-PIGS IN-VIVOAND IN-VITRO

The characteristics of airway responsiveness to acetylcholine (ACh) in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensiti ve (BHR) guinea pigs were clarified in vivo and in vitro. We measured the change in ventilatory mechanics in response to ACh inhalation by m eans of the bodyplethysmograph and the contractile responses of isolat ed trachea to ACh and carbachol (CCh). Further, muscarinic receptor su btypes involved these responses were identified The basal values for v entilatory mechanics in BHS were not significantly different from thos e in BHR. Respiratory resistance to ACh was progressively increased in a time- and dose-dependent manner in BHS. The contractile responses o f tracheal smooth muscle to ACh in BHS were significantly greater than those in BHR, but CCh-induced responses in BHS and BHR were similar. ACh- and CCh-induced contractions were mediated via M-3 receptors. The se results suggested that the falling-down of BHS in response to ACh i nhalation was caused by the strong constriction of the airway and the reduction in ventilation. Moreover, the airway hyperresponsiveness to ACh in BHS might be partly dependent on the change in acetylcholineste rase activity.