Endothelial cellshave a pivotal role in the control of vascular homeostasis, in part, by releasing potent vasodilators such as nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and protacyclin (PGI2).The most important one is NO,which is generated from L-arginine by the enzyme termed endothelial NO synthase.NO also strongly inhibits platelet activation and prothrombotic and pro-atherosclerotic responses.An endothelial dysfunction characterized by a reduced generation of these endotheliumdependent vasodilators associated to vascular oxidative stress and the formation of endothelium-dependent contracting factors such as contractile prostanoids is often observed in most types of cardiovascular diseases, and physiological ageing.Nutritional-derived polyphenols from a variety of fruits, tea and cocoa increase the endothelial formation of NO by causing the redox-sensitive Src/PI3-kinase/Aktdependent activation of endothelial NO synthase leading to a sustained formation of NO.Moreover, these polyphenols are also able to both improve an established ageing-related endothelial dysfunction and retard the induction of ageing-related endothelial dysfunction in the rat.The protective effect is mostly due to their ability to reduce vascular oxidative stress by inhibiting the overexpression of NADPH oxidase and the angiotensin system.Thus, nutritional-derived polyphenols may be an interesting approach to retard ageing-related endothelial dysfunction and, hence, the initiation and development of cardiovascular diseases.