Prostacyclin: its biosynthesis, actions and clinical potential

Abstract

Prostacyclin (PGI ₂ ) is the product of arachidonic acid metabolism generated by the vessel wall of all mammalian species studied, including man. Prostacyclin is a potent vasodilator and the most potent inhibitor of platelet aggregation so far described. Prostacyclin inhibits aggregation through stimulation of platelet adenyl cyclase leading to an increase in platelet cyclic AMP. In the vessel wall, the enzyme that synthesizes prostacyclin is concentrated in the endothelial layer. Prostacyclin can also be a circulating hormone released from the pulmonary circulation. Based on these observations we proposed that platelet aggregability in vivo is controlled via a prostacyclin mechanism. The discovery of prostacyclin has given a new insight into arachidonic acid metabolism and has led to a new hypothesis about mechanisms of haemostasis. Reductions in prostacyclin production in several diseases, including atherosclerosis and diabetes, have been described and implicated in the pathophysiology of these diseases. Additionally, since prostacyclin powerfully inhibits platelet aggregation and promotes their disaggregation, this agent could have an important use in the therapy of conditions in which increased platelet aggregation takes place and in which, perhaps, a prostacyclin deficiency exists. Prostacyclin has been used beneficially in humans during extracorporeal circulation procedures such as cardiopulmonary bypass, charcoal haemoperfusion and haemodialysis. Its possible use in other conditions such as peripheral vascular disease or transplant surgery is at present being investigated.