Involvement of arachidonate cyclooxygenase products in bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) in guinea pigs.
Effects of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) were investigated in anesthetized, artificially ventilated guinea pigs in order to examine the role of the cyclooxygenase pathway in bronchial hyperresponsiveness. Pretreatment with aerosolized OKY-046 significantly inhibited the bronchial hyperresponsiveness to histamine, but pretreatment with intravenous indomethacin showed a tendency to potentiate bronchial hyperresponsiveness. These results suggest that subthreshold concentration of thromboxane A2 contributes to bronchial hyperresponsiveness through activating the cyclooxygenase pathway including thromboxane A2 synthesis, and that the released cyclooxygenase products have an inhibitory effect on the bronchial hyperresponsiveness in guinea pigs.
Saito
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Fujimura
M
M
Sakamoto
S
S
Miyake
Y
Y
Shintani
H
H
Yasui
M
M
Matsuda
T
T
D000336:Aerosols; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000201:enzymology* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology
D000336:Aerosols; D008689:Methacrylates; D013928:Thromboxane A2; C037866:STA 2; C034364:ozagrel; D007213:Indomethacin