REPEATED ANTIGEN CHALLENGE INDUCED AIRWAY HYPERRESPONSIVENESS TO NEUROKININ A AND VAGAL NONADRENERGIC, NONCHOLINERGIC (NANC) STIMULATION IN GUINEA-PIGS

The effect of repeated weekly antigen challenges by aerosol on bronchopulmonary responses to ACh, histamine, neurokinin A or atropine-resistant (NANC) component of vagal stimulation, has been studied in guinea pigs. Bronchospastic responses were measured in anaesthetized animals, 7 days after the last challenge with antigen (or vehicle). No difference was observed between control and antigen challenged guinea pigs in their responsiveness to acetylcholine (1-300-mu-mol kg-1 i.v.) or histamine (1-300-mu-mol kg-1 i.v.).On the other hand, amplitude of bronchospasm induced by neurokinin A (1 - 3-mu-mol kg-1 i.v.) or NANC vagal stimulation (20 Hz, 1 msec, 10 V, trains of 5-20 sec) was significantly increased in guinea pigs previously challenged with antigen, as compared to controls. These results suggest that repetitive antigen exposure in sensitized guinea pigs generates an increase in the responsiveness to exogenously administered or endogenously released tachykinins, at a time when no generalized hyperresponsiveness to other spasmogens could be observed.