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

Publication ,  Journal Article
Grześk, G; Kozinski, M; Tantry, US; Wicinski, M; Fabiszak, T; Navarese, EP; Grzesk, E; Jeong, Y-H; Gurbel, PA; Kubica, J
Published in: Biomed Res Int
2013

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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Published In

Biomed Res Int

DOI

EISSN

2314-6141

Publication Date

2013

Volume

2013

Start / End Page

928271

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Ticagrelor
  • Tail
  • Rats
  • Myocytes, Smooth Muscle
  • Muscle Contraction
  • Male
  • Endothelium, Vascular
  • Dose-Response Relationship, Drug
  • Aspirin
 

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Grześk, G., Kozinski, M., Tantry, U. S., Wicinski, M., Fabiszak, T., Navarese, E. P., … Kubica, J. (2013). High-dose, but not low-dose, aspirin impairs anticontractile effect of ticagrelor following ADP stimulation in rat tail artery smooth muscle cells. Biomed Res Int, 2013, 928271. https://doi.org/10.1155/2013/928271
Grześk, Grzegorz, Marek Kozinski, Udaya S. Tantry, Michal Wicinski, Tomasz Fabiszak, Eliano P. Navarese, Elzbieta Grzesk, Young-Hoon Jeong, Paul A. Gurbel, and Jacek Kubica. “High-dose, but not low-dose, aspirin impairs anticontractile effect of ticagrelor following ADP stimulation in rat tail artery smooth muscle cells.Biomed Res Int 2013 (2013): 928271. https://doi.org/10.1155/2013/928271.
Grześk G, Kozinski M, Tantry US, Wicinski M, Fabiszak T, Navarese EP, et al. High-dose, but not low-dose, aspirin impairs anticontractile effect of ticagrelor following ADP stimulation in rat tail artery smooth muscle cells. Biomed Res Int. 2013;2013:928271.
Grześk, Grzegorz, et al. “High-dose, but not low-dose, aspirin impairs anticontractile effect of ticagrelor following ADP stimulation in rat tail artery smooth muscle cells.Biomed Res Int, vol. 2013, 2013, p. 928271. Pubmed, doi:10.1155/2013/928271.
Grześk G, Kozinski M, Tantry US, Wicinski M, Fabiszak T, Navarese EP, Grzesk E, Jeong Y-H, Gurbel PA, Kubica J. High-dose, but not low-dose, aspirin impairs anticontractile effect of ticagrelor following ADP stimulation in rat tail artery smooth muscle cells. Biomed Res Int. 2013;2013:928271.

Published In

Biomed Res Int

DOI

EISSN

2314-6141

Publication Date

2013

Volume

2013

Start / End Page

928271

Location

United States

Related Subject Headings

  • Vasoconstriction
  • Ticagrelor
  • Tail
  • Rats
  • Myocytes, Smooth Muscle
  • Muscle Contraction
  • Male
  • Endothelium, Vascular
  • Dose-Response Relationship, Drug
  • Aspirin