[Inhibitory effect of S-1452, a specific thromboxane A2 receptor antagonist on the increase of airway responsiveness in dogs after ozone exposure]

Abstract

We evaluated the inhibitory effect of S-1452, a specific thromboxane (Tx) A2 receptor antagonist on the increase of airway responsiveness in 7 dogs after ozone exposure. Airway responsiveness to inhaled methacholine (Mch) was determined by Astograph (7 Hz oscillation technique), and at the same time TxB2, 6-keto-prostaglandin (PG) F1 alpha, PGE2 levels and total cell counts in the bronchoalveolar lavage fluid (BALF) were measured. Ozone exposure was carried out for 2 hr at an ozone level of 3.04 +/- 0.02 ppm (mean +/- SEM). Airway responsiveness to Mch increased significantly after ozone exposure (p less than 0.01), and this hyperresponsiveness was inhibited significantly by pretreatment with S-1452 (p less than 0.02). TxB2 and PGE2 levels in BALF did not change after ozone exposure, but the levels of 6-keto-PGF1 alpha decreased significantly after ozone exposure (p less than 0.05). Total cell counts in BALF increased significantly after ozone exposure (p less than 0.02). The decrease of 6-keto-PGF1 alpha levels and the increase of total cell counts were not affected by pretreatment with S-1452. These results suggest that S-1452 is protective against the increase of airway responsiveness induced by ozone exposure, and that TxA2 plays an important role in the hyperresponsiveness. But hyperresponsiveness may not be induced by hyperproduction of TxA2, but by the relative increase of TxA2 to PGI2.