Pharmacological model for airway hypersensitivity produced by propranolol and reserpine in guinea pigs.
Combined treatment with propranolol and reserpine enhanced acetylcholine-induced dose-response curves for bronchoconstriction in guinea pigs in vivo. This airway hyperreactivity model was investigated pharmacologically. (1) Increased capillary permeability and increases in leukocytes in bronchoalveolar lavage fluid (BALF) were not observed after this combined treatment. (2) The increased airway sensitivity to acetylcholine produced by propranolol and reserpine was inhibited by ketotifen and theophylline, reported in clinical studies to inhibit airway hyperreactivity. (3) Two leukotriene (LT) receptor antagonists, MCI-826 and FPL-55712, clearly inhibited this increased airway reactivity. (4) A thromboxane A2 (TXA2) receptor antagonist, ONO-3708, and TXA2 synthetase inhibitor, OKY-046, also inhibited this increased airway reactivity. These results suggest that the airway hyperreactivity model produced by propranolol and reserpine in guinea pigs is a valuable pharmacological tool for investigating a remedy and LT and TXA2 may be involved in the onset of this airway hyperreactivity.
Goto
S
S
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Nagai
H
H
Inagaki
N
N
Koda
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D004357:Drug Synergism; D006168:Guinea Pigs; D007665:Ketotifen / Q000494:pharmacology; D007958:Leukocyte Count; D020024:Leukotriene Antagonists; D008297:Male; D008954:Models, Biological; D011433:Propranolol / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000503:physiopathology; D013806:Theophylline / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
D020024:Leukotriene Antagonists; D013928:Thromboxane A2; D012110:Reserpine; D011433:Propranolol; D013806:Theophylline; D000109:Acetylcholine; D007665:Ketotifen