AIRWAY HYPERREACTIVITY OR HYPOREACTIVITY TO INHALED SPASMOGENS 24 H AFTER OVALBUMIN CHALLENGE OF SENSITIZED GUINEA-PIGS

1 The aim of this study was to determine whether an inhalation of oval bumin (OA, 10 or 20 mg ml(-1)) by conscious OA-sensitized guinea-pigs leads to airway hyperreactivity to spasmogens 24 h later. In contrast to most previous studies, the spasmogens (5-HT, methacholine (MCh), U- 46619 and adenosine) were administered by inhalation and airway functi on was measured in conscious guinea-pigs. 2 Guinea-pigs were sensitize d by i.p. injection of 10 mu g OA and 100 mg aluminium hydroxide in 1 mi normal saline; 14-21 days later they were exposed to an inhalation of 5-HT, MCh, U-46619 or adenosine. Specific airway conductance (sG(aw )) was measured in conscious animals by whole body plethysmography. Th e spasmogens caused bronchoconstriction, measured as a reduction in sG (aw) from the pre-inhalation basal values. Dose-related bronchoconstri ctions were observed with 5-HT, MCh and U-46619. 3 The effect of an ov albumin macroshock challenge upon the responses to each spasmogen were examined by giving an inhalation of aerosolized OA at 24 h (or 7 days in the case of adenosine) after an initial spasmogen challenge. Eight een to twenty-four hours after the OA macroshock, the same guineapigs were exposed to a repeated inhalation of 5-HT, MCh, U-46619 or adenosi ne. 5 All results were compared with a control group of sensitized gui nea-pigs receiving a NaCl challenge. The bronchoconstrictor responses to 5-HT, MCh, U-46619 or adenosine did not differ signifcantly before and after the saline challenge, indicating reproducibility of the resp onses. 6. 6 In further experiments, guinea-pigs were exposed to inhala tion of 5-HT (50 mu g ml(-1)) or MCh (300 mu g ml(-1)) 24 h before atr opine (10 mu g, 100 mu g or 1 mg ml(-1)) and again at 0.5 to 1.5 h aft erwards. Atropine antagonized the 5-HT- and MCh-induced bronchoconstri ctions over the same antagonist dose-range. This suggests that the bro nchoconstriction induced in the conscious guinea-pig by 5-HT is mediat ed primarily via muscarinic receptors, possibly by a vagal reflex. The inhibition of the responses to 5-HT and MCh by OA challenge would the refore appear to be related to interference with a common cholinergic pathway for these spasmogens. 7 In summary, airway hyperresponsiveness was evident at 24 h after OA challenge as measured by an enhanced bro nchoconstrictor response to inhaled U-46619. When 5-HT or MCh were use d as the spasmogens, an opposing decrease in responsiveness was observ ed. This was presumed to be due to an inhibition of cholinergic pathwa ys by the OA challenge. Adenosine caused a bronchoconstriction in the sensitized animals but this was not enhanced by the OA challenge.