sta-2 and Airway-Obstruction

U-46619, a thromboxane A(2) (TXA(2)) mimetic, is shown to cause airway microvascular leakage, although the effects is weak when comparing with that to induce bronchoconstriction in guinea pigs.. In order to know the airway effect of TXA(2) more accurately, we have examined the effects of STA(2), a TXA(2) mimetic with higher affinity to TXA(2) (TP) receptors than U-46619, to induce airway microvascular leakage and airflow obstruction.. Anesthetized and ventilated guinea pigs were i.v. given STA(2) (3-30 nmol/kg) or U-46619 (3-100 nmol/kg) 1 min after i.v. Evans blue dye. STA(2)- and U-46619-induced increases in lung resistance (R(L)) was measured for 6 min. The amount of extravasated Evans blue dye in the lower airways was, then, examined as an index of leakage. In selected animals, specific TP receptor antagonists (10 microg/kg S-1452 or 10 mg/kg ONO-3708) were pretreated i.v.. Both STA(2) and U-46619 induced significant increases in leakage and airflow obstruction. However, STA(2) induced a slow and significantly less increase in R(L) but caused a significantly greater increase in extravasation of Evans blue dye compared to U-46619. Specific TP receptor antagonists completely abolished both airway effects induced by STA(2) and U-46619.. Our present results have supported a possibility that TXA(2) induces microvascular leakage as well as bronchoconstriction in the airways.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Airway Obstruction; Airway Resistance; Animals; Blood Pressure; Bridged Bicyclo Compounds; Capillary Permeability; Dose-Response Relationship, Drug; Evans Blue; Extravasation of Diagnostic and Therapeutic Materials; Fatty Acids, Monounsaturated; Guinea Pigs; Lung; Male; Platelet Aggregation Inhibitors; Thromboxane A2; Time Factors; Vasoconstrictor Agents