Red Wine Induced Modulation of Vascular Function: Separating the Role of Polyphenols, Ethanol, and Urates

Abstract

By using red wine (RW), dealcoholized red wine (DARW), polyphenols-stripped red wine (PSRW), ethanol-water solution (ET), and water (W), the role of wine polyphenols, ethanol, and urate on vascular function was examined in humans (n = 9 per beverage) and on isolated rat aortic rings (n = 9). Healthy males randomly consumed each beverage in a cross-over design. Plasma ethanol, catechin, and urate concentrations were measured before and 30, 60 and 120 minutes after beverage intake. Endothelial function was assessed before and 60 minutes after beverage consumption by normalized flow-mediated dilation (FMD). RW and DARW induced similar vasodilatation in the isolated vessels whereas PSRW, ET, and W did not. All ethanol-containing beverages induced similar basal vasodilatation of brachial artery. Only intake of RW resulted in enhancement of endothelial response, despite similar plasma catechin concentration after DARW. The borderline effect of RW on FMD (P = 0.0531) became significant after FMD normalization (P = 0.0043) that neutralized blunting effect of ethanol-induced basal vasodilatation. Effects of PSRW and ET did not differ although plasma urate increased after PSRW and not after ET, indicating lack of urate influence on endothelial response. Acute vascular effects of RW, mediated by polyphenols, cannot be predicted by plasma catechin concentration only.

Grape products and cardiovascular disease risk factors

“…In human subjects, an improvement in endothelium-dependent vasodilatation has been reported after the acute intake of white wine or red wine with a meal by subjects with IHD (54) ; also it has been observed that an acute intake of red grape polyphenol extract, red wine or dealcoholised red wine cause an increase in flow-mediated dilatation, peaking at 60 min (54,55) . Nevertheless, in another study (53) red wine, but not polyphenols from red wine, produced an enhancement of endothelial response, despite a similar catechin concentration in both products. Intake of grape juice or grape seed extract for 2-3 weeks also caused a significant increase in flow-mediated dilatation, compared with the control group (56,57) .…”

“…Also, these effects on the development of atheromatous plaque were presumably due not only to their antioxidant effects, but also to inhibition of cell proliferation in smooth muscle, regulation of adhesion molecules and reduction of the flux of atherogenic molecules from the endothelium to the arterial wall (52,53) .…”

“…In studies in animals, red wine polyphenols induced endothelium-dependent relaxation in rat aorta (49) , red wine and dealcoholised red wine induced vasodilatation in isolated vessels from rats (53) and grape skin extract had a vasodilator effect on the mesenteric cardiovascular bed of rats (42) . In human subjects, an improvement in endothelium-dependent vasodilatation has been reported after the acute intake of white wine or red wine with a meal by subjects with IHD (54) ; also it has been observed that an acute intake of red grape polyphenol extract, red wine or dealcoholised red wine cause an increase in flow-mediated dilatation, peaking at 60 min (54,55) .…”

“…Also, grape polyphenols may have a reducing effect in cardiac fibrosis, a process occurring in cases of hypertension (17) Thirty-five healthy women 4 weeks Red wine with 13·5 % ethanol and 1·9 g total polyphenols/l or white wine with 13 % ethanol and 0·31 g total polyphenols/l Agewall et al (2000) (18) Twelve healthy subjects Acute intake Red wine with 1·9 g total polyphenols/l and 12·5 % ethanol or dealcoholised red wine with 1·1 g total polyphenols/l (250 ml in all groups) Cross-over design Naissides et al (2004) (19) Seventeen postmenopausal women Acute intake Dealcoholised red wine with 2·2 g total polyphenols/l, white wine with 2·2 g total polyphenols/l or water Cross-over design Williams et al (2004) (20) Fourteen men with stable IHD Acute intake Red wine with 13·5 % ethanol and 1·2 g total polyphenols/l, white wine with 13 % ethanol and 0·2 g total polyphenols/l or non-alcoholic drink without polyphenols Cross-over design Pignatelli et al (2006) (21) Twenty healthy subjects 3 weeks Red wine with 12·5 % ethanol and 1·2 g total polyphenols/l or white wine with 12·5 % ethanol and 0·18 g total polyphenols/l Castilla et al (2008) (24) Thirty-two haemodialysed patients 2 weeks Red grape concentrate (100 ml/d ¼ 600 mg total polyphenols/d), 800 IU (20 mg) vitamin E/d or both De Rijke et al (1996) (25) Twenty-four healthy subjects 2 weeks, then 4 weeks with different treatments (33) Nine hypercholesterolaemic and eight normocholesterolaemic subjects (45) Hypertensive men 8 weeks Grape juice with 2·1 g total polyphenols/l or placebo (11 ml/kg weight per d in all groups) Ward et al (2005) (46) Hypertensive subjects 6 weeks Vitamin C, polyphenols from red grape seeds (1 g/d), both or control Chou et al (2001) (47) Fifteen healthy subjects 1 week Extract from grape peel with 5 % total polyphenols (600 mg extract/d) Matsuo et al (2001) (51) Six men Acute intake Red wine, ethanol, polyphenols from red wine Cross-over design Freedman et al (2001) (52) Twenty healthy volunteers 2 weeks Purple grape juice (7 ml/kg weight per d) Boban et al (2006) (53) Nine men Acute intake Red wine, dealcoholised red wine, polyphenols from red wine, ethanol -water solution, water Cross-over design Whelan et al (2004) (10...…”

Red Wine and Cardiovascular Health

“…3 In addition, red wine and dealcoholized red wine increase flow-mediated vasodilation of the brachial artery in healthy subjects. 4,5 Intake of red wine also counteracts endothelial dysfunction produced by high-fat diet in human volunteers, 6 and red wine increases flow-mediated vasodilation and decreases blood pressure in adult cigarette smokers.…”