Primary hemostasis is determined by the interaction between platelets and the vessel wall. Platelet reactivity with the vessel wall has been shown to be regulated by the balance of opposing actions of unstable arachidonic acid metabolites on the platelet: prostaglandin I2 (PGI2) from vascular endothelial cells and thromboxane A2 from platelets, the opposing effects of which on the platelet are mediated by changes in platelet cyclic AMP levels. There is almost no information, however, on the regulation of endothelial PGI2 production and, specifically, reciprocal control mechanisms exerted by the platelet on the endothelial cell. This will be investigated with cultured human and bovine endothelial cells. I plan to explore the response of endothelial cells to prostaglandins, the ability of prostaglandins to modulate endothelial adenylate cyclase and the physiologic effects of cyclic AMP in regulating endothelial PGI2 synthesis. I will then turn to the effects platelets on these endothelial activities in experiments which will bring platelets in contact with endothelial cells: specifically, the effects of both arachidonic acid oxygenation pathways of activated platelets (cyclooxygenase and lipoxygenase) will be dissected. The aim of these studies is to lay the groundwork for an integrated model of platelet-endothelial interaction. An understanding of the normal regulatory mechanisms involved in this system is needed before we can explore failures which result in thrombosis and vascular disease.