Inhibition of acute platelet thrombosis formation in stenosed canine coronary arteries by specific serotonin 5HT2 receptor antagonist ritanserin. 1990

S Torr, and M I Noble, and J D Folts
Department of Medicine, University of Wisconsin Hospital and Clinics, Madison.

OBJECTIVE The aim of the study was to test the hypothesis that platelet serotonin 5HT2 receptors are important in the genesis of thrombosis in stenosed coronary arteries. METHODS The specific serotonin 5HT2 receptor antagonist, ritanserin was used as a pharmacological tool to examine the effect of removal of the participation of the 5HT2 receptors on thrombus growth, in a paired statistical design. METHODS The study involved 10 open chest anaesthetised dogs, with constrictors of critical diameter applied to the left circumflex coronary artery. RESULTS Blood flow was monitored in the left circumflex coronary arteries, distal to the critical stenosis. Flow reductions occurred that have previously been shown to be caused by the accumulation of platelet thrombi. By embolising the thrombi, the process could be monitored cyclically (cyclic flow reductions). The specific serotonin 5HT2 receptor antagonist, ritanserin, abolished cyclic flow reductions at a dose of 0.5 mg.kg-1. There was no effect on blood pressure or heart rate on administration of ritanserin at any dose. The serotonin blockade by ritanserin also prevented the reestablishment of cyclic flow reductions by adrenaline infusion (0.4 micrograms.kg-1.min-1), but required ritanserin doses up to 1.5 mg.kg-1. Ex vivo aggregation of platelets was reduced in blood taken from the dogs after ritanserin administration. CONCLUSIONS These results constitute further evidence of the possible importance of serotonin as a mediator of platelet thrombosis in stenosed coronary arteries.

UI MeSH Term Description Entries
D008297 Male Males
D010880 Piperidines A family of hexahydropyridines.
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
D003327 Coronary Disease An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. Coronary Heart Disease,Coronary Diseases,Coronary Heart Diseases,Disease, Coronary,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Heart,Heart Disease, Coronary,Heart Diseases, Coronary
D003328 Coronary Thrombosis Coagulation of blood in any of the CORONARY VESSELS. The presence of a blood clot (THROMBUS) often leads to MYOCARDIAL INFARCTION. Thrombosis, Coronary,Coronary Thromboses,Thromboses, Coronary
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004837 Epinephrine The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS. Adrenaline,4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol,Adrenaline Acid Tartrate,Adrenaline Bitartrate,Adrenaline Hydrochloride,Epifrin,Epinephrine Acetate,Epinephrine Bitartrate,Epinephrine Hydrochloride,Epinephrine Hydrogen Tartrate,Epitrate,Lyophrin,Medihaler-Epi,Acetate, Epinephrine

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