Abstract:
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 weremeasured 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: Pretreatmentwith 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.
