Objective. To compare effects of low- versus high-dose aspirin coadministered with ticagrelor on the reactivity of vascular\r\nsmooth muscle cells (VSMCs). Methods.Wistar rats were orally administered ticagrelor (10mg/kg) and/or aspirin (2 or 10mg/kg)\r\nn = 7 per each of 4 groups) or placebo (n = 9) 12 and 2 hours before experiments. Anticontractile effects of ticagrelor\r\nwere assessed in perfusion solution containing ticagrelor (1 ??M/L). Changes in perfusion pressure proportional to the degree\r\nof adenosine diphosphate analogue- (2-MeS-ADP-) and phenylephrine-induced constriction of rat tail arteries were evaluated.\r\nResults. Pretreatment with high- but not low-dose aspirin enhanced the reactivity of VSMCs only in endothelium-lined vessels.\r\nSuppression of 2-MeS-ADP-induced VSMC contraction by ticagrelor observed in arteries with and without endothelium was\r\nmaintained in endothelialized arteries pretreated only with low-dose aspirin. For endothelium-denuded vessels and low-dose\r\naspirin we observed a significant reduction of the maximal effect of ticagrelor with no rightward shift of the concentration-response\r\ncurve for phenylephrine.With high-dose aspirin pretreatment ticagrelor exerted no anticontractile effect. Conclusion. High-dose,\r\nbut not low-dose, aspirin impairs the anticontractile effect of ticagrelor on ADP-induced VSMC contraction in the rat model. Both\r\nthe clinical significance and detailed underlying mechanism of our findings require further investigation.
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