AIRWAY REACTIVITY TO INHALED SPASMOGENS 18-24-HOUR AFTER ANTIGEN-CHALLENGE IN SENSITIZED ANESTHETIZED GUINEA-PIGS

The anaesthetized allergic guinea-pig was used to assess changes in ai rway reactivity to four different inhaled spasmogens: methacholine, 5- hydroxytryptamine (5-HT), histamine and the thromboxane A(2) mimetic, 9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF(2 alpha) (U-46619). Re activity was determined 18 to 24 h after challenge of ovalbumin-sensit ized guinea-pigs with inhaled ovalbumin. This time coincides with the appearance of a late-phase bronchoconstriction in these animals. Sensi tivity to the spasmogen was assessed from the concentration-response c urve for the increase in pulmonary inflation pressure (PIP) in ovalbum in-and saline-challenged sensitized animals. When methacholine, 5-HT o r histamine were the spasmogens there was no hyper-reactivity. The geo metric mean EC50 values (i.e. the concentrations inducing half the max imum effect) obtained from the dose-response curves for methacholine ( 73 (42-129) and 94 (66-134) mu g mL(-1)), 5-HT (1.5 (0.81-3.03) and 1. 1 (0.51-2.24 mu g mL(-1)) and histamine (39 (21-75) and 72 (32-162) mu g 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 si gnificantly (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 a bsence of hyper-reactivity with certain spasmogens was not a result of poor delivery, because all spamogens caused a bronchoconstriction by the inhaled route. It was also not associated with the model because o zone has been shown to induce hyper-reactivity to inhaled methacholine and 5-HT. Because airway hyper-reactivity to both inhaled histamine a nd agonists at muscarinic receptors is regularly seen in man, the anae sthetized guinea-pig might not be the ideal model for assessing airway hyper-reactivity after antigen challenge and its modification by anti -asthma drugs.