Inhibitory effect of inhalation of a thromboxane synthetase inhibitor on bronchoconstriction induced by aerosolized leukotriene C4 and thromboxane A2 analogue in anesthetized guinea pigs.
Effect of aerosol administration of a thromboxane synthetase inhibitor (OKY-046) on bronchoconstriction induced by aerosol leukotriene C4, histamine and a thromboxane A2 analogue (STA2) was studied in anesthetized, artificially ventilated guinea pigs in order to evaluate the effectiveness of inhalation of OKY-046 on an unfavorable mechanism of secondary release of thromboxane A2. 0.01-1.0 micrograms/ml leukotriene C4, 25-400 micrograms/ml histamine and 0.033-1.0 micrograms/ml STA2 inhaled from an ultrasonic nebulizer developed for small animals caused a dose-dependent increase of pressure at the airway opening (Pao), which is considered to be an index representing bronchial response. Pretreatment of the animals with aerosol OKY-046 (0.035 and 0.35 mg/animal) significantly reduced the airway responses produced by inhalation of leukotriene C4 and STA2, in a dose-dependent manner, while the pretreatment did not affect the histamine dose-response curve. These findings suggest that aerosol leukotriene C4 and STA2 activate thromboxane synthesis in the airway, and inhalation of OKY-046 may be useful for preventing the secondary release of thromboxane A2, which is an unfavorable mechanism in asthma.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Ogawa
H
H
Saito
M
M
Sakamoto
S
S
Miyake
Y
Y
Matsuda
T
T
D000280:Administration, Inhalation; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D013189:SRS-A / Q000008:administration & dosage*; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D008689:Methacrylates; D013189:SRS-A; D013928:Thromboxane A2; C037866:STA 2; D013930:Thromboxane-A Synthase; C034364:ozagrel