Involvement of PAF in postallergic propranolol-induced bronchoconstriction in guinea-pigs.
Administration of propranolol can provoke bronchoconstriction in asthmatic patients. Recently, we successfully developed a guinea-pig model for propranolol-induced bronchoconstriction (PIB). We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. The purpose of this study was to examine the role of platelet-activating factor (PAF) in the development of PIB after allergic reaction. Propranolol, at a concentration of 10 mg.mL-1 was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially-ventilated guinea-pigs. The animals were treated intravenously with PAF antagonists, E6123 (1 and 10 micrograms.kg-1) or Y-24180 (1 and 10 mg.kg-1), 10 min before or 15 min after antigen challenge. Propranolol inhaled 20 min after antigen challenge caused bronchoconstriction. E6123 and Y-24180 administered 15 min after antigen challenge as well as 10 min before antigen challenge reduced the PIB in a dose-dependent manner. We conclude that platelet-activating factor may contribute to the development of propranolol-induced bronchoconstriction after allergic reaction in our guinea-pig model.
Third Dept of Internal Medicine, Kanazawa University School of Medicine, Japan.
M
M
Fujimura
M
M
Tsujiura
N
N
Songür
S
S
Myou
T
T
Matsuda
D000280:Administration, Inhalation; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D000768:Anesthesia, General; D000818:Animals; D000941:Antigens; D001249:Asthma / Q000503:physiopathology; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000503:physiopathology*; D007114:Immunization; D018836:Inflammation Mediators / Q000502:physiology; D007275:Injections, Intravenous; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011433:Propranolol / Q000008:administration & dosage / Q000009:adverse effects*; D012121:Respiration, Artificial; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000941:Antigens; D001381:Azepines; D018836:Inflammation Mediators; D010972:Platelet Activating Factor; D014230:Triazoles; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; C068033:E 6123; D011433:Propranolol