sta-2 and ozagrel

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.

Topics: Aerosols; Animals; Asthma; Bronchial Hyperreactivity; Bronchoconstriction; Dose-Response Relationship, Drug; Guinea Pigs; Indomethacin; Male; Methacrylates; Thromboxane A2

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.

Topics: Administration, Inhalation; Animals; Bronchoconstriction; Dose-Response Relationship, Drug; Guinea Pigs; Injections, Intraperitoneal; Male; Methacrylates; SRS-A; Thromboxane A2; Thromboxane-A Synthase

We examined vascular thromboxane A2 (TXA2) generation and its relation to a proliferation of vascular smooth muscle cells (VSMCs) in spontaneously hypertensive rats (SHRs). Aortic TXA2 release was significantly enhanced in 5-week-old SHRs, as compared with Wistar-Kyoto strain rats (WKY). The cultured VSMCs of SHRs exhibited a shorter doubling time and a greater [3H]thymidine uptake than those of WKY rats. OKY 046 a thromboxane synthetase inhibitor, tempered proliferation of VSMCs in SHRs, but not in WKY rats. STA2, a stable analog of TXA2, stimulated VSMC growth in WKY rats more than in SHRs. It is indicated that vascular TXA2 generation is enhanced, and partially participates in the rapid proliferation of VSMCs in SHRs.

Topics: Animals; Blood Vessels; Cell Division; Hypertension; In Vitro Techniques; Methacrylates; Muscle, Smooth, Vascular; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thromboxane A2; Thromboxane-A Synthase