Ticagrelor, but not clopidogrel and prasugrel, prevents ADP-induced vascular smooth muscle cell contraction: A placebo-controlled study in rats
| Autor: | Eliano Pio Navarese, Marek Koziński, Elzbieta Grzesk, Jolanta M. Siller-Matula, Marek Krzyżanowski, Fausto Castriota, Grzegorz Grzesk, Aldona Kubica, Jacek Kubica |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Ticagrelor
Vasopressin Adenosine Ticlopidine Prasugrel Vascular smooth muscle Myocytes Smooth Muscle Thiophenes Pharmacology Piperazines ticagrelor P2Y12 vascular smooth muscle cells Animals Medicine Rats Wistar Phenylephrine off-target effect clopidogrel business.industry Arteries Hematology Clopidogrel prasugrel Rats Adenosine Diphosphate platelets Purinergic P2Y Receptor Antagonists business Prasugrel Hydrochloride Perfusion Platelet Aggregation Inhibitors Muscle Contraction medicine.drug |
| Zdroj: | Thrombosis Research. 130:65-69 |
| ISSN: | 0049-3848 |
| Popis: | Introduction Off-target effects of novel antiplatelet agents due to their potential clinical benefits are currently an area of intensive investigation. We aimed to compare the effects of different P2Y12 antagonists on the reactivity of vascular smooth muscle cells. Materials and methods Wistar rats (n = 30) were pretreated with an investigated drug or placebo. Clopidogrel (50 mg/kg, n = 7), prasugrel (10 mg/kg, n = 7), ticagrelor (10 mg/kg, n = 7) or placebo (n = 9) were administered orally 12 and 2 hours before experiments. Constrictions of rat tail arteries induced with a stable analogue of adenosine diphosphate (2-MeS-ADP), phenylephrine and arginine vasopressin were measured as an increase in perfusion pressure. Effects of ticagrelor were assessed in the presence of ticagrelor (1 μM/L) added to the perfusion solution as this drug reversibly inhibits the P2Y12 receptor. Results Pretreatment with clopidogrel and prasugrel did not inhibit 2-MeS-ADP-induced contraction while ticagrelor did. Experiments employing endothelium-deprived arteries provided similar results. Clopidogrel and prasugrel did not influence concentration-response curves in the presence of neither phenylephrine nor arginine vasopressin. The curves obtained for both vasopressors in the presence of ticagrelor and 2-MeS-ADP were shifted to the right with a significant reduction in the maximal response. Conclusions Oral administration of ticagrelor, in contrast to clopidogrel and prasugrel, prevents adenosine diphosphate-induced contraction of vascular smooth muscle cells in a rat model. Both the clinical significance and detailed mechanism of our findings warrant further investigation. |
| Databáze: | OpenAIRE |
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