Bradykinin-induced release of thromboxane B2 into bronchoalveolar lavage fluid of guinea pigs: relationship to airflow obstruction.
The aim of this study was to evaluate the role of thromboxane A2 in bradykinin-induced airflow obstruction in guinea pig in vivo. Airway insufflation pressure (Pi) was measured to assess airflow obstruction and the thromboxane B2 (a stable metabolite of thromboxane A2) concentration in bronchoalveolar lavage fluid was determined by radioimmunoassay. The animals were pretreated with propranolol (1 mg/kg i.v.) and suxamethonium (5 mg i.v.) prior to bradykinin administration. Bradykinin instillation into the trachea (300 nmol) induced a Pi increase (47.5 +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thromboxane B2 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-propenoic acid hydrochloride mono-hydrate)) or a thromboxane A2 receptor antagonist (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 Pi increase evoked by bradykinin (38.7 +/- 3.8 and 40.6 +/- 3.8 cm H2O, respectively). OKY-046 abolished the thromboxane B2 release. A platelet-activating factor receptor antagonist, WEB2086 (1 mg/kg i.v.; (3-[4-(chlorophenyl)-9-methyl-6H-thienol [3,2-f][1,2,4]trizolo-[4,3-a][1,4] diazepin-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 A2 release.
Kawikova
I
I
Department of Clinical Pharmacology, Göteborg University, Sweden.
Arakawa
H
H
Petersson
M
M
Löfdahl
C G
CG
Skoogh
B E
BE
Lötvall
J
J
D000402:Airway Obstruction / Q000209:etiology* / Q000503:physiopathology; D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D007278:Injections, Spinal; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000008:administration & dosage / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D011863:Radioimmunoassay; D013390:Succinylcholine / Q000008:administration & dosage / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D001381:Azepines; D004146:Dioxanes; D008689:Methacrylates; D009467:Neuromuscular Depolarizing Agents; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D014665:Vasodilator Agents; C052518:WEB 2086; C057498:ICI 192605; D013929:Thromboxane B2; D011433:Propranolol; D013930:Thromboxane-A Synthase; D013390:Succinylcholine; C034364:ozagrel; D001920:Bradykinin