Grape pomace enzymatic extract restores vascular dysfunction evoked by endothelin-1 and DETCA via NADPH oxidase downregulation and SOD activation

Grape pomace enzymatic extract (GP-EE) exhibits a potent antioxidant and vasodilator activity, although the mechanisms underlying this action are not completely understood. Our aim was to evaluate its vasoactive mechanisms, focusing on vascular NADPH oxidase and superoxide dismutase (SOD)-dependent pathways. GP-EE effectively restored vascular impairment induced by the NADPH oxidase activator endothelin-1 through downregulation of its Nox-1 and p47phox subunits. GP-EE partially prevented endothelial dysfunction elicited by the SOD inhibitor, DETCA, preserving EC-SOD and Mn-SOD isoenzymes protein expression. Although many of these vasoactive effects could be attributed to the presence of catechin, GP-EE was able to exert additional protection against the vascular deleterious effects evoked by NADPHox activation and SOD inhibition. This additional vasoprotection could be related to the enzymatic extraction process, providing polyphenols from winemaking residue with a potent activity against vascular dysfunction by preventing NADPHox activation and maintaining SOD defense, making GP-EE as an ideal nutritional supplement.