THE EFFECTS OF A KININ ANTAGONIST ON CHANGES IN LUNG-FUNCTION AND PLASMA EXTRAVASATION INTO THE AIRWAYS FOLLOWING CHALLENGE OF SENSITIZED GUINEA-PIGS

Background It has been suggested that kinins may play a role in allerg ic pathophysiology of the airways, contributing to bronchoconstriction and oedema formation. Raised levels of kinin generating enzymes and k inins are found in the airways during allergic responses. Objective Us ing an in vivo animal model of allergen induced increase in airways re sistance we investigated the effects of the bradykinin antagonist Hoe 140, in order to assess the possible contribution of kinins to this re sponse. Methods Guinea-pigs were sensitized and challenged with ovalbu min (OA) or saline via the endotracheal route and the resulting increa se in airways resistance was measured by whole body plethysmography. A t 240 min after challenge, bronchoalveolar lavage fluid (BALF) was tak en and albumin content and kallikrein-like activity determined by rock et immunoelectrophoresis and use of artificial substrates respectively . Pretreatment of animals with the bradykinin antagonist Hoe 140 at 6. 7, 20 or 66.7 nmol/kg or aprotinin (46 000 kallikrein inhibitor units/ kg) was by i.p. injection 10 min before challenge. Results Pre-treatme nt with Hoe 140 dose dependently attenuated the increase in airways re sistance following allergen challenge. Kallikrein-like activity and al bumin in BALF were unaltered. Aprotinin reduced the kallikrein-like ac tivity in BALF but did not alter airways resistance. Conclusion Kinins may contribute to a significant part of allergen-induced airways resi stance increase in this model but not via an effect on plasma extravas ation.