INFLUENCE OF SPASMOGEN INHALATION BY GUINEA-PIGS UPON SUBSEQUENT DEMONSTRATION OF OVALBUMIN-INDUCED HYPERREACTIVITY IN ISOLATED AIRWAYS TISSUES

Guinea pigs were sensitized with ovalbumin (i.p.) 14 days before use. In vivo airway hyperreactivity induced by ovalbumin inhalation was det ermined by challenging with aerosolized spasmogen (5 -hydroxytryptamin e [5-HT] methacholine, the thromboxane -mimetic, U-46619, or adenosine ) 24 hr before (7 days with adenosine) and again 18-24 hr after the ov albumin inhalation. One hour later they were killed and isolated airwa ys perfused lung halves and tracheal spirals were set up for determina tion of tissue sensitivity to carbachol, histamine, and adenosine. Thi s study examines whether the spasmogen interferes with the ovalbumin-i nduced in vitro hyperreactivity and the combined effects of ovalbumin followed by spasmogen challenge upon tissue sensitivity. The influence of the spasmogen upon the in vitro measurement of ovalbumin-induced h yperreactivity was variable, depending upon which spasmogen was used a nd whether the lung or trachea was examined. The inhalation of the spa smogen in ovalbumin-challenged guinea pigs had clear effects upon the subsequent measurement of tissue sensitivity. This depended upon the s pasmogen used, but 5-HT, methacholine, and U-46619 usually depressed r esponsiveness, while adenosine was without significant effect. As a co nsequence, the appearances of in vitro hyperreactivity due to the oval bumin challenge could be masked (e.g., bolus doses of agonist in the t rachea when 5-HT was the spasmogen) or the degree of hyperreactivity c ould be enhanced (e.g., in the perfused lung when adenosine was the sp asmogen). Thus, isolated airways tissues should not be used for evalua ting tissue sensitivity when the animals have been previously exposed to inhalations of spasmogens.