Prostacyclin: its biosynthesis, actions and clinical potential

Abstract

Prostacyclin (PGI2) 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.

Genetic and Epigenetic Regulation of the Human Prostacyclin Synthase Promoter in Lung Cancer Cell Lines

“…The biological effects of these two prostaglandins are generally antagonistic to each other. PGI2 is anti-inflammatory, a strong vasodilator, an inhibitor of growth of vascular smooth muscle cells, and a potent inhibitor of platelet aggregation (4). In contrast, PGE2 is proinflammatory, induces proliferation, and is antiapoptotic (5).…”

Liver preservation: The past and the future

“…Nine groups of PGs have been identified and assigned the letter designations A through I, followed by a subscript denoting the number of carbon-carbon double bonds outside the ring. The latest-discovered PG, PGI,, has been shown to possess a variety of interesting biological activities, including inhibition of platelet aggregation, vasodilatation, stabilization of lysosomal membranes and increase of blood flow to the splanchnic region (116)(117)(118). All these effects, which are also attributed to PGE,, may play a role in the hepatocytoprotective properties of PGs.…”

“…Therefore other theories of the mechanism of action of PGs are required. In this respect it is proposed that the cytoprotective action of PGs is related to the well-established mechanism of platelet aggregation inhibition: PGI, and PGE, stimulate platelet adenyl cyclase, leading to an increase in platelet CAMP (117). As shown above, CAMP may play a key role in preventing liver harvest injury in an intricate interaction with Ca' ' and calmodulin (120).…”

Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation

“…The endothelium releases vasodilatory substances including nitric oxide (NO), prostacyclin, C-type natriuretic peptide and endothelium-derived hyperpolarizing factor, as well as vasoconstrictors including endothelin-1, angiotensin II and thromboxane A 2 (Needleman et al, 1976;Moncada & Vane, 1981;Vanhoutte & Katusic, 1988;Yanagisawa et al, 1988;Danser et al, 1994). In the healthy endothelium, a balanced production of these factors plays an important preventative role against vascular disease.…”