Effects of STA2, a Thromboxane A2 Mimetic, in Inducing Airflow Obstruction and Airway Microvascular Leakage in Guinea Pigs

Background: U-46619, a thromboxane A2 (TXA2) mimetic, is shown to cause airway microvascular leakage, although the effects is weak when comparing with that to induce bronchoconstriction in guinea pigs. Objective: In order to know the airway effect of TXA2 more accurately, we have examined the effects of STA2, a TXA2 mimetic with higher affinity to TXA2 (TP) receptors than U-46619, to induce airway microvascular leakage and airflow obstruction. Methods: Anesthetized and ventilated guinea pigs were i.v. given STA2 (3–30 nmol/kg) or U-46619 (3–100 nmol/kg) 1 min after i.v. Evans blue dye. STA2- and U-46619-induced increases in lung resistance (RL) 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 µg/kg S-1452 or 10 mg/kg ONO-3708) were pretreated i.v. Results: Both STA2 and U-46619 induced significant increases in leakage and airflow obstruction. However, STA2 induced a slow and significantly less increase in RL 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 STA2 and U-46619. Conclusion: Our present results have supported a possibility that TXA2 induces microvascular leakage as well as bronchoconstriction in the airways.