How do dietary flavanols improve vascular function? A position paper

Epidemiological and clinical studies revealed that high-flavanol diet or isolated (-)-epicatechin improves the function of the vascular endothelium, as assessed by flow-mediated dilation, through elevation of bioavailability and bioactivity of NO center dot. We have demonstrated that exposure of human endothelial cells to (-)-epicatechin elevates the cellular levels of NO center dot and cyclic GMP and protects against oxidative stress elicited by proinflammatory agonists. (-)-Epicatechin acts like a prodrug, since these effects involve O-methylation of the flavanol and are attributed to apocynin-like inhibition of endothelial NADPH oxidase. Thus, generation of superoxide and peroxynitrite is diminished and, consequently, the cellular NO center dot level is preserved or augmented. We propose therefore that endothelial NO center dot metabolism rather than general antioxidant activity is a major target of dietary flavanols and that NADPH oxidase activity is a crucial site of action. Moreover, flavonoid glucuronides appear to serve as plasma transport metabolites to target cells Father than solely as excretion products. Implications for the interpretation of the role of dietary polyphenols for cardiovascular health are discussed. (C) 2008 Elsevier Inc. All rights reserved.