Role of leukotrienes in post-allergic propranolol-induced bronchoconstriction in guinea-pigs.
BACKGROUND
Administration of propranolol can provoke bronchoconstriction only in asthmatic patients. Recently we developed an animal model for propranolol-induced bronchoconstriction (PIB). Our working hypothesis is that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction.


OBJECTIVE
Our goal in this study was to determine which products of arachidonate 5-lipoxygenase pathway are involved in the PIB.


METHODS
Propranolol at a concentration of 10 mg/mL was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea-pigs. Two different sulfidopeptide leukotriene (s-LT) antagonists, ICI198 615 in the doses of 0.03 and 0.3 mg/kg and vehicle and KCA757 in the doses of 1 and 5 mg/kg and vehicle, and a LTB4 antagonist ONO4057 in the doses of 1 and 10 mg/kg and vehicle were injected intravenously 15 min after antigen challenge. Effects of an anticholinergic agent atropine sulphate (5mg/kg) and an alpha-adrenergic blocker phentolamine (0.3 and 3 mg/kg) were examined in the same way.


RESULTS
Bronchoconstriction occurred when 10 mg/mL of propranolol was inhaled 20 min after antigen challenge. Both ICI198 615 and KCA757 administered intravenously 15 min after antigen challenge reduced the PIB in a dose-dependent manner while ONO4057 did not alter the PIB. Atropine or phentolamine did not change the PIB.


CONCLUSIONS
These results suggest that mediator mechanism, but not cholinergic or alpha-adrenergic nerve, is important in the PIB which developed after the allergic bronchoconstriction in our guinea-pig model and that s-LTs but not LTB4 have an important role in the pathophysiology of the PIB.
Fujimura
M
M
The Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Songür
N
N
Ishiura
Y
Y
Mizuhashi
K
K
Myou
S
S
Matsuda
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology*; D006168:Guinea Pigs; D006969:Hypersensitivity, Immediate / Q000188:drug therapy / Q000276:immunology*; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000276:immunology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000276:immunology*
D000317:Adrenergic alpha-Antagonists; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D018727:Muscarinic Antagonists; D001285:Atropine; D010047:Ovalbumin; D011433:Propranolol; D010646:Phentolamine