High-dose, but not low-dose, aspirin impairs anticontractile effect of ticagrelor following ADP stimulation in rat tail artery smooth muscle cells.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • GrzeĊ›k, G; Kozinski, M; Tantry, US; Wicinski, M; Fabiszak, T; Navarese, EP; Grzesk, E; Jeong, Y-H; Gurbel, PA; Kubica, J

Published Date

  • 2013

Published In

Volume / Issue

  • 2013 /

Start / End Page

  • 928271 -

PubMed ID

  • 23841099

Pubmed Central ID

  • PMC3690229

Electronic International Standard Serial Number (EISSN)

  • 2314-6141

Digital Object Identifier (DOI)

  • 10.1155/2013/928271


  • eng

Conference Location

  • United States