Key result
High-dose, but not low-dose, aspirin impaired the anticontractile effect of ticagrelor on ADP-induced vascular smooth muscle cell contraction in a rat model.
Why the study?
Does high-dose versus low-dose aspirin coadministered with ticagrelor impair the anticontractile effect of ticagrelor in rat tail artery smooth muscle cells?
Does high-dose versus low-dose aspirin coadministered with ticagrelor impair the anticontractile effect of ticagrelor in rat tail artery smooth muscle cells?
In a rat model, high-dose but not low-dose aspirin impairs the anticontractile effect of ticagrelor on ADP-induced vascular smooth muscle cell contraction.
Does not support changing aspirin dosing with ticagrelor; leaves open relevance to human vascular outcomes.
OBJECTIVE: To compare effects of low- versus high-dose aspirin coadministered with ticagrelor on the reactivity of vascular smooth muscle cells (VSMCs). METHODS: Wistar rats were orally administered ticagrelor (10 mg/kg) and/or aspirin (2 or 10 mg/kg) (n = 7 per each of 4 groups) or placebo (n = 9) 12 and 2 hours before experiments. Anticontractile effects of ticagrelor were assessed in perfusion solution containing ticagrelor (1 μM/L). Changes in perfusion pressure proportional to the degree of adenosine diphosphate analogue- (2-MeS-ADP-) and phenylephrine-induced constriction of rat tail arteries were evaluated. RESULTS: Pretreatment with high- but not low-dose aspirin enhanced the reactivity of VSMCs only in endothelium-lined vessels. Suppression of 2-MeS-ADP-induced VSMC contraction by ticagrelor observed in arteries with and without endothelium was maintained in endothelialized arteries pretreated only with low-dose aspirin. For endothelium-denuded vessels and low-dose aspirin we observed a significant reduction of the maximal effect of ticagrelor with no rightward shift of the concentration-response curve for phenylephrine. With high-dose aspirin pretreatment ticagrelor exerted no anticontractile effect. CONCLUSION: High-dose, but not low-dose, aspirin impairs the anticontractile effect of ticagrelor on ADP-induced VSMC contraction in the rat model. Both the clinical significance and detailed underlying mechanism of our findings require further investigation.
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Grześk et al. (2013) studied Vascular smooth muscle cell reactivity (n=37). Ticagrelor and aspirin vs. Placebo was evaluated on Changes in perfusion pressure proportional to the degree of 2-MeS-ADP- and phenylephrine-induced constriction of rat tail arteries. High-dose, but not low-dose, aspirin impaired the anticontractile effect of ticagrelor on ADP-induced vascular smooth muscle cell contraction in a rat model.
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