In vitro inhibition of human cGMP-specific phosphodiesterase-5 by phenols from red grapes

Epidemiological studies have shown a putative correlation between moderate consumption of red wine and lowered risk of coronary heart disease. Red wine represents a rich source of phenolics such as anthocyanins (ACs), catechins, proanthocyanidins (PAs), stilbenes (trans-resveratrol, and the corresponding 3-O-β-glucoside, trans-piceid), hydroxycinnamates (HCs) and other phenolics. Biological mechanisms proposed for red wine-derived phenolic compounds include estrogenic activity, antioxidant/antiradical activity, inhibition of platelet aggregation, modulation of lipid metabolism, inhibition of low density lipoprotein oxidation and proliferation of smooth muscle cells (SMC) (Dell’Agli, 2004). Last, but not least, wine polyphenols exhibit vasorelaxing effects, mainly through NO-dependent mechanisms. The studies concerning the relaxing effects of wine polyphenols on the arterial wall focused on mechanisms mediated by NO release (Dell’Agli, 2004), while other possible mechanisms such as the inhibition of phosphodiesterases (PDEs) in the SMC were never considered. Indeed, rat thoracic aortic rings could be relaxed by red wine-derived phenolic compounds also when functional endothelium was removed, and the anthocyanin-enriched fractions were the most active at this regard (Andriambeloson, 1998). cGMP-specific PDE5 in vascular SMC regulates cGMP levels and consequently the duration and extent of vasorelaxation (Beavo, 1995). Thus, the present work investigated whether vasorelaxation by red wine-derived phenolic compounds could also be related to the PDE inhibition; for this purpose, wine and grape polyphenols were tested on cGMP dependent PDE5, using a recombinant form of human PDE5A1 isoenzyme