Red wine polyphenols cause endothelium-dependent EDHF-mediated relaxations in porcine coronary arteries via a redox-sensitive mechanism.
Moderate consumption of wine is associated with cardiovascular protection most likely by increasing the endothelial formation of nitric oxide (NO). The present study investigated whether red wine polyphenolic compounds (RWPCs) increase the formation of endothelium-derived hyperpolarizing factor (EDHF) in arteries and, if so, to characterize the underlying mechanism. Porcine coronary artery rings were suspended in organ chambers for measurement of changes in isometric tension and membrane potential in the presence of indomethacin and N(omega)-nitro-L-arginine. RWPCs caused pronounced endothelium-dependent relaxations and hyperpolarizations, which were reduced by the combination of charybdotoxin plus apamin (two inhibitors of EDHF-mediated responses). Both responses to RWPCs were also reduced by antioxidants, membrane permeant analogues of superoxide dismutase, and diphenylene iodonium, an inhibitor of flavin-dependent enzymes. RWPCs induced the formation of superoxide in cultured endothelial cells. These findings demonstrate that RWPCs cause EDHF-mediated relaxations of coronary arteries, which are critically dependent on a redox-sensitive mechanism involving a flavin-dependent enzyme.
Ndiaye
Mamadou
M
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, Strasbourg, France.
Chataigneau
Thierry
T
Andriantsitohaina
Ramaroson
R
Stoclet
Jean-Claude
JC
Schini-Kerth
Valérie B
VB
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001685:Biological Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010084:Oxidation-Reduction; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D014664:Vasodilation; D014920:Wine
D001685:Biological Factors; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D017382:Reactive Oxygen Species; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin