Effect of red wine on endothelium-dependent relaxation in rabbits.

1. Published data on the effects of red wine, ethanol and flavonoids on endothelium-dependent relaxation are equivocal. The present study was undertaken to determine the effects of red wine, ethanol and selected flavonoids present in red wine on endothelium-dependent relaxation. 2. Aortic rings from New Zealand White rabbits were set up in organ baths (20 ml) and contracted with noradrenaline (10(-6) mol/l). An attempt was made to elicit dose-dependent relaxant responses to red wine (15, 30, 40, 80 or 120 microliters), ethanol (5.4, 10.8 and 16.2 microliters) and the flavonoids catechin, epicatechin, quercetin and polymeric phenols (10(-7) to 10(-4) mol/l). In some experiments, endothelium-dependent relaxation to cumulative doses of acetylcholine (10(-9) to 10(-6) mol/l) was determined before and after incubating the rings for 15 min with red wine (120 microliters), ethanol (16.2 microliters), quercetin (10(-5) mol/l), catechin (10(-5) mol/l), epicatechin (10(-5) mol/l) and PPs (10(-5) mol/l) respectively. cGMP was also measured in some rings in the control state and after addition of 120 microliters of red wine, sodium nitroprusside (10(-4) mol/l) and polymeric phenols (10(-5) mol/l). 3. Red wine evoked a dose-dependent relaxation in aortic rings. The highest volumes of wine (120 microliters) relaxed the vessels by 71.35 +/- 7.89% of the maximal contraction (8.95 +/- 0.97 g). Polymeric phenols also relaxed the precontracted rings. These responses were abolished by NG-L-arginine methyl ester (L-NAME) and by removal of endothelium. Addition of red wine, polymeric phenols and sodium nitroprusside increased the cGMP content of the rings. In tissues previously incubated with red wine and polymeric phenols, endothelium-dependent relaxation in response to acetylcholine was attenuated. Ethanol had no such effect. 4. Acute exposure of aortic rings to red wine and polymeric phenols evokes an endothelium-dependent relaxation which is mediated by nitric oxide. However, prior exposure to both red wine and polymeric phenols has a second effect in that it attenuates the endothelium-dependent relaxation evoked by acetylcholine. Since this effect is restored by arginine, it is likely to be due to depletion of substrate for nitric oxide synthase.