Prostaglandins in the pathogenesis and prevention of vascular disease

Abstract

Metabolism of arachidonic acid gives rise to a number of products with potent, and sometimes opposing, biological actions. Prostacyclin, the main product of arachidonic acid in vascular tissue, is a vasodilator and inhibitor of platelet aggregation whereas thromboxane A2, produced by the platelet, is a vasoconstrictor and inducer of platelet aggregation. Generation of these products may be modified in certain diseases, such as atherosclerosis and diabetes, so that prostacyclin production is reduced and thromboxane A2 production increased, resulting in a pro-thrombotic condition. Synthesis of arachidonic acid metabolites may be manipulated using drugs such as aspirin or imidazole analogues which selectively inhibit different enzymes in the metabolic pathway. Such drugs have proved beneficial in the treatment of some vascular disorders. Clinical use of prostacyclin has shown it to be effective in the treatment of peripheral vascular disease, Raynaud's Syndrome and pulmonary hypertension. Stable analogues of prostacyclin are being developed which may lead to a separation of the vasodilator and anti-platelet actions of prostacyclin.