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 vasorelaxation 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), was also investigated. 2. Relaxation produced by polyphenols was studied in rat aortic rings with and without functional endothelium, pre-contracted to the same extent with noradrenaline (0.3 and 0.1 microM, respectively). RWPC and leucocyanidol, but not catechin, produced complete relaxation of vessels with and without endothelium. However, 1000 fold higher concentrations were needed to relax endothelium-denuded rings compared to those with functional endothelium. 3. High concentrations of catechin (in the range of 10(-1) gl-1) only produced partial relaxation (maximum 30%) and had the same potency in rings with and without endothelium. 4. The NO synthase inhibitor, N omega-nitro-L-arginine-methyl-ester (L-NAME, 300 microM) completely abolished the endothelium-dependent 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 concentration-response curve for the NO donor, SIN-1 (3-morpholino-sydnonimine) which also produces superoxide anion (O2-). 6. In aortic rings with endothelium, RWPC (10(-2) gl-1) produced, a 7 fold increase in the basal production of guanosine 3':5'-cyclic monophosphate (cyclic GMP) which was prevented by L-NAME (300 microM). 7. Electron paramagnetic resonance (e.p.r.) spectroscopy studies with Fe(2+)-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 abolished by L-NAME (300 microM). 8. These results show that RWPC and leucocyanidol, but not the structurally closely related polyphenol catechin, induced endothelium-dependent relaxation in the rat aorta. They indicate that this effect results from enhanced synthesis of NO rather than enhanced biological activity of NO or protection against breakdown by O2. It is concluded that some polyphenols, with specific structure, contained in wine possess potent endothelium-dependent vasorelaxing activity.
Andriambeloson
E
E
Laboratoire de Pharmacologie et Physiopathologie Cellulaires, Universite Louis Pasteur de Strasbourg, URA CNRS 600 Faculté de Pharmacie, France.
Kleschyov
A L
AL
Muller
B
B
Beretz
A
A
Stoclet
J C
JC
Andriantsitohaina
R
R
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002392:Catechin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation; D014920:Wine
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010636:Phenols; D011108:Polymers; D009569:Nitric Oxide; D002392:Catechin; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; C001532:leucocyanidin; D019331:NG-Nitroarginine Methyl Ester