ROLE OF KININS IN ANAPHYLACTIC-INDUCED BRONCOCONSTRICTION MEDIATED BY TACHYKININS IN GUINEA-PIGS

1 In the present study, we have investigated the role of kinins in allergen-induced bronchoconstriction. 2 Anaesthetized guinea-pigs were sensitized to ovalbumin, ventilated artificially, pretreated with atropine (1.4 mu mol kg(-1), i.v.) and total pulmonary resistance (R(L)) measured. In preliminary studies in the presence of the neutral endopeptidase inhibitor, phosphoramidon (4.5 mu mol kg(-1), i.v.), the bradykinin B-2 receptor antagonist Hoe 140 (0.1 mu mol kg(-1), i.v.) completely abolished the increase in R(L) following aerosolized bradykinin (1 mM, 40 breaths), but had no effect on the increase in R(L) following aerosolized neurokinin A (NKA, 10 mu M, 40 breaths). On the other hand, a combination of the NK1 (CP-96,345, 2 mu mol kg(-1), i.v.) and NK2 (SR 48968, 0.3 mu mol kg(-1), i.v.) tachykinin receptor antagonists abolished completely the increase in R(L) produced by NKA and partially inhibited the increase in R(L) produced by bradykinin. These results confirm previous studies that suggest that bradykinin induces the release of tachykinins from sensory nerves in guinea-pig airways. 3 Aerosolized ovalbumin (0.5%, 5 breaths) increased R(L) in sensitized guinea-pigs pretreated with atropine (1.4 mmol kg(-1), i.v.), an effect that began within 2 min and reached a maximum within 5 min; R(L) remained above baseline at 20 min. Pretreatment with the bradykinin B-2 receptor antagonist, Hoe 140, decreased the bronchoconstrictor effect of ovalbumin markedly at 10 to 20 min. In the presence of phosphoramidon (4.5 mu mol kg(-1), i.v.) the inhibition induced by Hoe 140 was apparent earlier and remained over the 20 min period of study. 4 Pretreatment with a combination of NK1 (CP-96,345) and NK2 (SR 48968) tachykinin receptor antagonists also markedly inhibited ovalbumin-induced bronchoconstriction; addition of the bradykinin B-2 receptor antagonist to the NK1 and NK2 tachykinin receptor antagonists had no additional inhibitory effect on antigen-induced bronchoconstriction. 5 These findings confirm that activation of sensory nerves to release tachykinins in guinea-pig airways contribute to antigen-induced bronchoconstriction, and provide evidence that tachykinin release is due to kinins generated during the allergic response.