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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 516017, 11 pages
Research Article

Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II

1UMR CNRS 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74 Route du Rhin, BP 60024, 67401 Illkirch, France
2Institut de Physiologie, Faculté de Médecine, EA 3072, 11 Rue Humann, 67000 Strasbourg, France
3Service de Physiologie et d’Explorations Fonctionnelles, Pôle de Pathologie Thoracique, NHC-1 Place de l’Hôpital, 67091 Strasbourg, France

Received 27 May 2013; Accepted 22 July 2013

Academic Editor: Yong Chool Boo

Copyright © 2013 Noureddine Idris-Khodja 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.


This study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO) and endothelium-derived hyperpolarization (EDH) in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs), a rich natural source of antioxidants. Male Wistar rats were assigned into 4 groups: control, RWPs, doxorubicin, and doxorubicin + RWPs. Vascular reactivity was assessed in organ chambers; the vascular formation of reactive oxygen species (ROS) using dihydroethidine and the expression levels of small and intermediate conductance calcium-activated potassium channels ( , ) and connexin 40 (Cx40), which are involved in EDH-type relaxations, endothelial NO synthase (eNOS), angiotensin II, and AT1 receptors by immunofluorescence. The doxorubicin treatment impaired EDH-mediated relaxations, whereas those mediated by NO were minimally affected. This effect was associated with reduced expression levels of , , and Cx40, increased expression levels of eNOS, angiotensin II, and AT1 receptors, and formation of ROS in mesenteric arteries. RWPs prevented both the doxorubicin-induced blunted EDH-type relaxations and the increased vascular oxidative stress, and they improved the expression levels of target proteins. These findings suggest that polyphenol-rich natural products might be of interest in the management of doxorubicin-induced vascular injury possibly by improving the vascular angiotensin system.