Peptide leukotrienes mediate acetaldehyde-induced bronchial hyper-responsiveness in guinea-pigs.
BACKGROUND
We previously reported that inhaled acetaldehyde, a metabolite of ethanol and a main factor in alcohol-induced asthma, causes bronchial hyper-responsiveness (BHR) in asthmatics. However, the mechanisms are unclear.


OBJECTIVE
The purpose of this study was to investigate a role of a peptide leukotriene (LT) in acetaldehyde-induced BHR.


METHODS
Effects of LT antagonists, ONO-1078 (0.1-1.0 mg/kg) and ICI-198, 615 (0.03-0.3 mg/kg), on acetaldehyde-induced bronchoconstriction and BHR to inhaled methacholine were examined using a modified Konzett-Rössler method in guinea pigs.


RESULTS
Acetaldehyde at 0.8 mg/ml, which failed to induce significant changes in Pao (pressure at the airway opening), enhanced an increase in Pao induced by subsequent inhalations of ascending doses (50-200 micrograms/ml) of methacholine, suggesting a potentiating effect of acetaldehyde on bronchial responsiveness. Although ONO-1078 had no inhibitory effect on bronchoconstriction caused by ascending doses (5.0-20 mg/ml) of acetaldehyde, ONO-1078 and ICI-198, 615 reduced the acetaldehyde-induced BHR.


CONCLUSIONS
Acetaldehyde causes BHR via LT release in guinea-pigs.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Ishikawa, Japan.
Myou
S
S
Amemiya
T
T
Tachibana
H
H
Kita
T
T
Matsuda
T
T
D000079:Acetaldehyde; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006168:Guinea Pigs; D007191:Indazoles / Q000494:pharmacology; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride
D018926:Anti-Allergic Agents; D002867:Chromones; D007191:Indazoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016210:Methacholine Chloride; C054217:ICI 198615; D004155:Diphenhydramine; D000079:Acetaldehyde; C047681:pranlukast