Platelet activation by low-density lipoprotein and serotonin: effects of calcium antagonists.
Epidemiological studies indicate that there are biological interrelationships between blood pressure and blood lipids that may influence the mechanisms whereby hypertension is associated with an increased risk of coronary artery disease. Serotonin (5-HT) and thromboxane A2, which are released from aggregating platelets, mediate platelet-induced vasoconstriction, which itself significantly contributes to coronary artery constriction in vivo. Platelet aggregatory response to serotonin is modulated by disparate effects of lipoprotein fractions. This corresponds to the recognized differences in degree of atherogenicity of low- (LDL) and high-density lipoprotein (HDL). Amplification of serotonin-induced platelet aggregation by LDL and its inhibition by HDL support the hypothesis that 5-HT-mediated effects represent a mechanism clinically relevant to both chronic progression of atherosclerosis (particularly at sites of vascular injury and atherosclerotic plaques) and acute thrombotic events. Calcium antagonists differ in their platelet-inhibition potency, including their effects on platelet response to 5-HT and LDL. Verapamil and isradipine inhibit platelet aggregation induced by 5-HT at therapeutic concentrations. Isradipine also inhibits the amplifying effect of LDL on 5-HT-induced aggregation. These platelet effects of calcium antagonists appear to be neither group- nor class-specific but, rather, drug-specific.
Fetkovska
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Department of Clinical Pharmacology, Institute of Preventive and Clinical Medicine, Bratislava, Czechoslovakia.
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D008077:Lipoproteins, LDL; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin