Biomaterial Database

Insights into the role of thromboxane A2 and serotonin in the pathogenesis of unstable angina. 1994

A P Machado, and J A Saavedra, and C Ribeiro

Serviço de Medicina I, Hospitalar de Medicina Interna do Hospital de Santa Maria.

New research about platelet and endothelial functions is allowing us to better understand the pathogenesis of myocardial ischemic episodes in patients with unstable angina, creating new perspectives for the rational utilization of therapies. In patients with unstable angina, the episodes of symptomatic and silent ischemia are caused by repeated reductions of coronary blood flow. They are the result of the mechanical effect of the growing thrombus, which causes intermittent episodes of partial obstruction of the arterial lumen, in association with vasoconstriction at the stenotic site and dependent coronary arterial bed, produced by the cyclic release of platelet derived vasoactive products, namely thromboxane A2 and serotonin. Several studies, many of them in animal models of thrombosis, suggest that serotonin and thromboxane A2 are mediators of platelet aggregation, adynamic obstruction and coronary artery thrombosis. Because they cause coronary cyclic flow reductions, they are implicated in the pathogenesis of myocardial ischemic episodes during unstable angina. Drugs that interfere with the arachidonate pathway, and the 5-HT2-receptor antagonists, have been proven to decrease or abolish coronary cyclic flow variations in animal models and man. However, further studies should be done to test the hypothesis that the association of a 5-HT2-receptor antagonist with aspirin may contribute to decrease myocardial ischemia and prevent coronary occlusion in patients with unstable angina. Continuous Holter monitoring during the first week after admission in the hospital should be a good method to evaluate the eventual efficacy of this new class of drugs in abolishing or decreasing the frequency, intensity and duration of myocardial ischemic episodes in patients with unstable angina. The central role of serotonin in the pathogenesis of thrombotic events, and the presumed preventive effect of ketanserin, were the bases of a national multicenter pilot controlled study designed to evaluate the safety and efficacy of ketanserin plus aspirin in the secondary prevention of patients with unstable angina and non-Q wave myocardial infarction (KATUA Trial).

UI	MeSH Term	Description	Entries
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010974	Platelet Aggregation	The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.	Aggregation, Platelet
D010975	Platelet Aggregation Inhibitors	Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.	Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D011985	Receptors, Serotonin	Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.	5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D001792	Blood Platelets	Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.	Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D002986	Clinical Trials as Topic	Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.	Clinical Trial as Topic
D003326	Coronary Circulation	The circulation of blood through the CORONARY VESSELS of the HEART.	Circulation, Coronary
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000789	Angina, Unstable	Precordial pain at rest, which may precede a MYOCARDIAL INFARCTION.	Angina at Rest,Angina, Preinfarction,Myocardial Preinfarction Syndrome,Angina Pectoris, Unstable,Unstable Angina,Angina Pectori, Unstable,Anginas, Preinfarction,Anginas, Unstable,Myocardial Preinfarction Syndromes,Preinfarction Angina,Preinfarction Anginas,Preinfarction Syndrome, Myocardial,Preinfarction Syndromes, Myocardial,Syndrome, Myocardial Preinfarction,Syndromes, Myocardial Preinfarction,Unstable Angina Pectori,Unstable Angina Pectoris,Unstable Anginas