Wine polyphenols decrease blood pressure, improve NO vasodilatation, and induce gene expression.
The effects of short-term oral administration of red wine polyphenolic compounds on hemodynamic parameters and on vascular reactivity were investigated in rats. Endothelial function and vascular smooth muscle contractility were studied in association with the induction of gene expression in the vascular wall. Rats were treated daily for 7 days by intragastric administration of either 5% glucose or red wine polyphenolic compounds (20 mg/kg). Administration of these compounds produced a progressive decrease in systolic blood pressure, which became significantly different on day 4. Aortas from rats treated with red wine polyphenolic compounds displayed increased endothelium-dependent relaxation to acetylcholine that was related to increased endothelial NO activity and involved a mechanism sensitive to superoxide anion scavengers. However, no increase in whole-body oxidative stress has been observed in rats treated with red wine polyphenolic compounds, as shown by plasma glutathione assay. Also, in the aorta, red wine polyphenolic compounds increased the expression of cyclooxygenase-2 and increased the release of endothelial thromboxane A(2), which compensated for the extraendothelial NO-induced hyporeactivity in response to norepinephrine, resulting from enhanced inducible NO synthase expression. The present study provides evidence that short-term oral administration of red wine polyphenolic compounds produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with an enhanced endothelium-dependent relaxation and an induction of gene expression (of inducible NO synthase and cyclooxygenase-2) within the arterial wall, which together maintain unchanged agonist-induced contractility. These effects of red wine polyphenolic compounds may be a potential mechanism for preventing cardiovascular diseases.
Diebolt
M
M
Pharmacologie et Physicochimie des Interactions Cellulaires et Moléculaires, CNRS UMR 7034, Faculté de Pharmacie, Illkirch, France.
Bucher
B
B
Andriantsitohaina
R
R
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001158:Arteries / Q000378:metabolism / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects*; D015153:Blotting, Western; D046508:Culture Techniques; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000502:physiology; D005419:Flavonoids; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013929:Thromboxane B2 / Q000096:biosynthesis; D014664:Vasodilation / Q000187:drug effects*; D014920:Wine
D005419:Flavonoids; D007527:Isoenzymes; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; D009569:Nitric Oxide; D013929:Thromboxane B2; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases