NITRIC-OXIDE PRODUCTION AND ENDOTHELIUM-DEPENDENT VASORELAXATION INDUCED BY WINE POLYPHENOLS IN RAT AORTA

1 The aim of this work was to investigate the mechanism of vasorelaxat ion induced by red wine polyphenolic compounds (RWPC) and two defined polyphenols contained in wine, leucocyanidol and catechin. The role of the endothelium, especially endothelium-derived nitric oxide (NO), wa s also investigated. 2 Relaxation produced by polyphenols was studied in rat aortic rings with and without functional endothelium, pre-contr acted to the same extent with noradrenaline (0.3 and 0.1 mu M, respect ively). RWPC and leucocyanidol, but not catechin, produced complete re laxation of vessels with and without endothelium. However, 1000 fold h igher concentrations were needed to relax endothelium-denuded rings co mpared to those with functional endothelium. 3 High concentrations of catechin (in the range of 10(-1) g l(-1)) only produced partial relaxa tion (maximum 30%) and had the same potency in rings with and without endothelium. 4 The NO synthase inhibitor, N-omega-nitro-L-arginine-met hyl-ester (L-NAME, 300 mu M) completely abolished the endothelium-depe ndent but not the endothelium-independent relaxations produced by all of the polyphenolic compounds. 5 In contrast to superoxide dismutase ( SOD, 100 u ml(-1)), neither RWPC nor leucocyanidol affected the concen tration-response curve for the NO donor, SIN-1 (3-morpholino-sydnonimi ne) which also produces superoxide anion (O-2(-)) 6 In aortic rings wi th endothelium, RWPC (10(-2) g l(-1)) produced a 7 fold increase in th e basal production of guanosine 3':5'-cyclic monophosphate (cyclic GMP ) which was prevented by L-NAME (300 mu M). 7 Electron paramagnetic re sonance (e.p.r.) spectroscopy studies with Fe2+-diethyldithiocarbamate as an NO spin trap demonstrated that RWPC and leucocyanidol increased NO levels in rat thoracic aorta about 2 fold. This NO production was entirely dependent on the presence of the endothelium and was abolishe d by L-NAME (300 mu M). 8 These results show that RWPC and leucocyanid ol, but not the structurally closely related polyphenol catechin, indu ced endothelium-dependent relaxation in the rat aorta. They indicate t hat this effect results from enhanced synthesis of NO rather than enha nced biological activity of NO or protection against breakdown by O-2( -). It is concluded that some polyphenols, with specific structure, co ntained in wine possess potent endothelium-dependent vasorelaxing acti vity.