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BioMed Research International
Volume 2013 (2013), Article ID 928271, 8 pages
http://dx.doi.org/10.1155/2013/928271
Research Article

High-Dose, but Not Low-Dose, Aspirin Impairs Anticontractile Effect of Ticagrelor following ADP Stimulation in Rat Tail Artery Smooth Muscle Cells

1Department of Pharmacology and Therapeutics, Collegium Medicum, Nicolaus Copernicus University, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland
2Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland
3Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA
4Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Poland
5Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju, Gyeongsangnam-do 660-702, Republic of Korea

Received 2 March 2013; Accepted 13 May 2013

Academic Editor: Jeffrey L. Anderson

Copyright © 2013 Grzegorz Grześk et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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) ( per each of 4 groups) or placebo ( ) 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.