Thromboxane A2 in cardiovascular and renal disorders: is there a defined role for thromboxane receptor antagonists or thromboxane synthase inhibitors?
Thromboxane (TX) A2 and the prostaglandin endoperoxides, PGG2 and PGH2, have a number of biological activities including contraction of vascular and bronchial smooth muscle, platelet secretion and aggregation, and lysis of cellular membranes. Activation of TXA2 receptors may have deleterious consequences in various pathophysiologies, including coronary thrombosis, myocardial infarction, hypertension and renal injury. In addition to cyclooxygenase inhibitors, TX receptor antagonists and TX synthase inhibitors are available as specific pharmacological tools to investigate the specific involvement of TXA2 and the prostaglandin endoperoxides in these conditions. Recent reports indicate that these agents may be useful to prevent coronary artery thrombosis, prevent coronary artery reocclusion following thrombolytic therapy, attenuate the sequelae of circulatory shock, and improve kidney function after renal injury. This review will discuss the specific involvement of TX in these disorders, and compare the efficacy of different pharmacological approaches to the manipulation of either TX formation or activity.
Smith
E F
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Smith Kline and French Laboratories, Department of Pharmacology, King of Prussia, PA 19406.
D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000494:pharmacology / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000502:physiology
D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase