Physiologic and pathophysiologic role of cyclo-oxygenase metabolites of arachidonic acid in circulatory disease states.
The overall assessment of eicosanoids in ischemia and shock is complex. Certain prostaglandins, notably PGI2, actually improved survival in shock and ischemic states; however, some, including TxA2, act as mediators, significantly contributing to the pathophysiology of vasospasm and ischemia. This makes the intelligent use of eicosanoid-related drugs very difficult. Broad-based inhibitors (for example, cyclo-oxygenase inhibitors) are not likely to exert significant protective effects because they inhibit beneficial as well as detrimental eicosanoids. More appropriately, the therapy of ischemic disorders should be designed to employ specific agents (for example, TxSI and TxRA) rather than broad-based agents. Preliminary studies already suggest the success of such an approach. Future investigations will focus on the application of potent synthetic modulators or analogues of specific eicosanoids in an attempt to prevent the deleterious effects of eicosanoid mediators of ischemic disorders and to potentiate and prolong the beneficial actions of therapeutic eicosanoids.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001775:Blood Circulation; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003329:Coronary Vasospasm / Q000503:physiopathology; D003645:Death, Sudden; D003925:Diabetic Angiopathies / Q000473:pathology; D004537:Eicosanoic Acids / Q000378:metabolism; D011464:Epoprostenol / Q000502:physiology; D006439:Hemodynamics; D006801:Humans; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D013928:Thromboxane A2 / Q000502:physiology
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D011956:Receptors, Cell Surface; D016718:Arachidonic Acid; D013928:Thromboxane A2; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A