P-selectin (PADGEM protein, GMP-140 or CD 62) is a glycoprotein of platelet a-granules and endothelial Weibel-Palade bodies that, by mediating cellular adhesion, initiates recruitment of leukocytes and lymphocytes into injured tissue. Both of the endothelial antiplatelet autacoids prostacyclin (PGI(2)) and nitric oxide (NO) have been demonstrated to inhibit P-selectin expression. Prostaglandin endoperoxides PGG(2)/PGH(2) that are generated by activated platelets have been demonstrated to be used by endothelium for generation of prostacyclin. In an experimental model in vitro that resembles vessel wall/platelet/PMN interaction in vivo, we found that aspirin (100 μM), a COX inhibitor, but not L-NMMA (100 μM) and a NO-synthase inhibitor, reversed the inhibitory effect of arterial wall on P-selectin mediated platelet/PMN adhesion. The anti-adhesive potency of vessel wall reversed by aspirin was dose-dependently restored by camonagrel (3-100 μM), a new TXA(2) synthase inhibitor. We conclude that selective TXA(2)-synthase inhibitors may inhibit P-selectin mediated platelet/PMN adhesion by augmenting formation of prostacyclin by vessel walls.