Actively sensitised guinea-pigs were exposed to inhalation challenges with ovalbumin aerosol (macro-and microshock) and airway responsiveness to six intravenously administered spasmogens was evaluated 18 to 24 hr later in the anaesthetised animal. An increase in airway sensitivity was defined as a significant leftward shift of the dose-response curve when compared with saline-challenged control sensitized animals. After ovalbumin-macroshock (I% ovalbumin for 2 min. with mepyramine cover against fatal anaphylaxis), airway hyperresponsiveness was seen to 5-HT, the thromboxane A2-mimetic, U-46619, and bradykinin but not to methacholine, histamine or substance I? A similar pattern was seen after ovalbumin-microshock (0.01% ovalbumin for 60 min.). with induction of airway hyperreactivity to 5-HT and U-46619 but not methacholine or histamine. When the U-46619 dose-response curve was constructed following treatment of the animals with atropine (1 mgikg. intravenously), airway hyperresponsiveness was no longer significant. As an index of airway inflammation, lung weights were significantly heavier in ovalbumin-challenged animals, than in saline-challenged controls. The results of this study with intravenously administered spasmogens does not support claims that ovalbumininduced airway hyperreactivity in the guinea-pig is a 'non-specific' phenomenon.

The anaesthetized allergic guinea-pig was used to assess changes in airway reactivity to four different inhaled spasmogens: methacholine, 5-hydroxytryptamine (5-HT), histamine and the thromboxane A2 mimetic, 9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha (U-46619). Reactivity was determined 18 to 24 h after challenge of ovalbumin-sensitized guinea-pigs with inhaled ovalbumin. This time coincides with the appearance of a late-phase bronchoconstriction in these animals. Sensitivity to the spasmogen was assessed from the concentration-response curve for the increase in pulmonary inflation pressure (PIP) in ovalbumin- and saline-challenged sensitized animals. When methacholine, 5-HT or histamine were the spasmogens there was no hyper-reactivity. The geometric mean EC50 values (i.e. the concentrations inducing half the maximum effect) obtained from the dose-response curves for methacholine (73 (42-129) and 94 (66-134) micrograms mL-1), 5-HT (1.5 (0.81-3.03) and 1.1 (0.51-2.24 micrograms mL-1) and histamine (39 (21-75) and 72 (32-162) micrograms mL-1) did not differ significantly (P > 0.05) between saline- and ovalbumin-challenged animals, respectively. However, when U-46619 was the spasmogen, ovalbumin-induced airway hyper-reactivity was observed as a leftwards shift of the concentration-response curve and the EC50 value for ovalbumin-challenged animals (8.1 (5.1-13) ng mL-1) was significantly (P < 0.05) less than the value for control animals (39 (21-75) ng mL-1). Our findings suggest that airway hyper-reactivity is not 'non-specific', but instead depends on the chosen spasmogen. The absence of hyper-reactivity with certain spasmogens was not a result of poor delivery, because all spasmogens caused a bronchoconstriction by the inhaled route. It was also not associated with the model because ozone has been shown to induce hyper-reactivity to inhaled methacholine and 5-HT. Because airway hyper-reactivity to both inhaled histamine and agonists at muscarinic receptors is regularly seen in man, the anaesthetized guinea-pig might not be the ideal model for assessing airway hyper-reactivity after antigen challenge and its modification by anti-asthma drugs.

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