BRADYKININ-INDUCED RELEASE OF THROMBOXANE B-2 INTO BRONCHOALVEOLAR LAVAGE FLUID OF GUINEA-PIGS - RELATIONSHIP TO AIR-FLOW OBSTRUCTION

The aim of this study was to evaluate the role of thromboxane A(2) in bradykinin-induced airflow obstruction in guinea pig in vivo. Airway i nsufflation pressure (P-i) was measured to assess airflow obstruction and the thromboxane B-2 (a stable metabolite of thromboxane A(2)) conc entration in bronchoalvelolar lavage fluid was determined by radioimmu noassay. The animals were pretreated with propranolol (1 mg/kg i.v.) a nd suxamethonium (5 mg i.v.) prior to bradykinin administration. Brady kinin instillation into the trachea (300 nmol) induced a P-i increase (47.5 +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thro mboxane B-2 release into bronchoalveolar lavage fluid (79 +/- 19 pg/ml versus 19 +/- 6 in sham). A thromboxane synthase inhibitor (OKY-046, 30 mg/kg i.v.; ((E-E)-3-[p(1H-imidazole-1-yl-methyl) phenyl]-2-propeno ic acid hydrochloride mono-hydrate)) or a thromboxane A(2) receptor an tagonist (ICI192,605, 0.5 mg/kg i.v.; (4-(Z)-6-(2-o-chloro-phenyl-4-o- hydroxyphenyl 1,3-dioxan-cis-5-yl)hexenoic acid)) reduced the P-i incr ease evoked by bradykinin (38.7 +/- 3.8 and 40.6 +/- 3.8 cm H2O, respe ctively). OKY-046 abolished the thromboxane B-2 release. A platelet-ac tivating factor receptor antagonist, WEB2086 (1 mg/kg i.v.; (3-[4-(chl orophenyl)-9-methyl-6H-thienol [3,2-f][1,2,4]trizolo-[4,3-a][1,4] diaz epin-2-yl]1-4-(4-morpholinyl)-1-propanon) did not significantly affect any measured parameter. We conclude that, in guinea pigs, bradykinin- induced airway effects are associated with a local thromboxane A(2) re lease.