Interrelationships between prostacyclin and thromboxane A2.
Prostacyclin is a 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. It inhibits platelet aggregation through stimulation of adenylate cyclase leading to an increase in cyclic AMP in the platelets. The enzyme which synthesizes prostacyclin is mainly localized in the endothelial layer of the vascular wall. Prostacyclin can also be a circulating hormone constantly released by the pulmonary circulation. On the basis of these observations we proposed that platelet aggregability in vivo is controlled via a prostacyclin mechanism. In contrast to the vessel wall, in blood platelets arachidonic acid is converted by the enzyme thromboxane synthetase to a potent vasoconstrictor and proaggregating substance, thromboxane A2. Therefore arachidonic acid is metabolized in the vessel wall and the platelets to potent substances with opposing biological activities. The balance between the activities of these substances is important in the homeostatic interaction of the platelets and the vessel wall. The different ways of interfering with this balance and its impact in the development of thrombosis and atherosclerosis are discussed. The balance between thromboxane A2 and prostacyclin might be important in the control of the pulmonary circulation. This possibility is discussed in the light of the present evidence.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000378:metabolism* / Q000494:pharmacology; D013931:Thromboxanes / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
D001095:Arachidonic Acids; D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins; D013931:Thromboxanes; D013928:Thromboxane A2; D011464:Epoprostenol; D000242:Cyclic AMP; D001241:Aspirin