O38 The omega-3 EPA:DHA 6:1 formulation improves ageing-related blunted endothelium-dependent relaxations and increased contractile responses in the mesenteric artery: Role of oxidative stress and cyclooxygenases

Introduction Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to cause endothelium-dependent nitric oxide (NO)-mediated relaxations of isolated blood vessels, with EPA:DHA 6:1 being a superior formulation. The aim of the present study was to determine whether EPA:DHA 6:1 improves ageing-related endothelial dysfunction, and, if so, to determine the underlying mechanism. Methods Male Wistar rats (20 months-old) received daily 500 mg/kg of either EPA:DHA 6:1 (omega 3), corn oil (control), or water for 2 weeks. Young male Wistar rats (12 weeks-old) were used as a control. Results In the main mesenteric artery, ageing was associated with an endothelial dysfunction characterized by a blunted NO-mediated component, an abolished endothelium-dependent hyperpolarization (EDH)-mediated component, and also by the induction of endothelium-dependent contractile responses (EDCF, in the presence of NO and EDH inhibitors) sensitive to indomethacin (a cyclooxygenase inhibitor) in response to acetylcholine. Endothelial dysfunction was associated with an increased level of vascular oxidative stress and expression of COX-2, but not of COX-1, in the mesenteric artery. The EPA:DHA 6:1 treatment improved both the NO- and EDH-mediated relaxations, and reduced EDCF, vascular oxidative stress and expression of COX-2 in the old mesenteric artery. Conclusion The present findings indicate that intake of EPA:DHA 6:1 prevented the development of the ageing-related endothelial dysfunction in rats. The beneficial effect involves an improvement of both the NO- and the EDH-mediated relaxations as well as a reduction of endothelium-dependent contractile response most likely by preventing vascular oxidative stress.