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Reversal of doxorubicin-induced vascular dysfunction by resveratrol in rat thoracic aorta: Is there a possible role of nitric oxide synthase inhibition?

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Author(s): Murat Olukman | Cenk Can | Ayşe Erol | Gülperi Öktem | Onur Oral | Mehtap Gülcihan Çınar

Journal: Anadolu Kardiyoloji Dergisi
ISSN 1302-8723

Volume: 09;
Issue: 05;
Start page: 260;
Date: 2009;
Original page

Keywords: Doxorubicin | vascular endothelial function | nitric oxide | resveratrol | rat

ABSTRACT
Objective: The natural antioxidant, resveratrol has been suggested to protect against doxorubicin-induced cardiotoxicity. Although derangements in nitric oxide (NO) synthesis contribute to vascular endothelial dysfunction caused by doxorubicin, the effects of resveratrol on these parameters have not been evaluated yet. We investigated the impact of resveratrol on doxorubicin-induced vascular dysfunction in rat thoracic aorta with regard to NO synthesis in an experimental, prospective, controlled study. Methods: Wistar rats were assigned to 5 groups; doxorubicin (n=9), vehicle (dimethylsulphoxide) (n=8), resveratrol (n=8), doxorubicin+resveratrol (n=10), controls (n=9). Contractile and relaxant responses were evaluated on the isolated thoracic aortas. The expressions of endothelial (eNOS) and inducible (iNOS) isoforms of NO-synthase were also examined histopathologically on the aortas. Statistical analysis was performed by ANOVA for repeated measures for the response curves and one-way ANOVA for the pD2 (-log EC50) and Emax (maximum phenylephrine contraction) values with subsequent Bonferroni test.Results: Doxorubicin (20 mg/kg, i.p), not only decreased the contractile responses to phenylephrine (p
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