ARACHIDONIC-ACID METABOLITES AND THE INTERACTIONS BETWEEN PLATELETS AND BLOOD-VESSEL WALLS

Prostaglandins [PG] are potent vasoactive agents with a wide variety of other actions that depend on the species and organ tested and the PG used. Arachidonic acid is released from membrane phospholipids by the enzyme phospholipase A2, which can be activated by many different stimuli. Once released, arachidonic acid is rapidly metabolized into oxygenated products by 2 distinct pathways. The 1st pathway involves lipoxygenases. For many years it was believed that PGE2 and PGF2.alpha. were the main products of arachidonic acid metabolism. Particular attention was paid to the putative role of PGE2 in the inflammatory process. Aspirin-like drugs [which are antiinflammatory] in low concentrations inhibit cyclo-oxygenase, the very 1st enzyme in the cascade. Thus, aspirin has the capacity to reduce or abolish the formation of the endoperoxides and all their subsequent products. Isolation and identification of unstable intermediates in the metabolic pathway of arachidonic acid, i.e., prostaglandin endoperoxides PGG2 and PGH2, and thromboxane A2 and prostacyclin, have greatly increased understanding of the physiology of platelets and their interaction with the vessel wall. Thrombosis is discussed. Generation of prostacyclin appears to be the physiologic mechanism that protects the vessel wall from deposition of platelet aggregates and explains the long-recognized fact that contact of platelets with healthy vascular endothelium is not a stimulus for clumping.