Red Wine Polyphenols Enhance Endothelial Nitric Oxide Synthase Expression and Subsequent Nitric Oxide Release From Endothelial Cells

Abstract

Background-Population-based studies suggest a reduced incidence of morbidity and mortality from coronary heart disease caused by moderate and regular consumption of red wine. Endothelial nitric oxide (NO) is a pivotal vasoprotective molecule. This study examines the influence of red wine polyphenols on the regulation of endothelial nitric oxide synthase (eNOS) expression and subsequent NO synthesis, focusing on the putative long-lasting antiatherosclerotic effects of red wine. Methods and Results-Treatment (20 hours) of human umbilical vein endothelial cells (HUVECs) and of the HUVEC-derived cell line EA.hy926 with a alcohol-free red wine polyphenol extract (RWPE) led to a concentrationdependent (100 to 600 g/mL), significant increase in NO release (up to 3.0-fold/HUVEC and 2.0-fold/EA.hy926) as shown by use of the fluorescent probe DAF-2. This effect was corroborated by the [ 14 C]L-arginine/L-citrulline conversion assay in intact EA.hy926 cells. RWPE (20 hours, 100 to 600 g/mL) also significantly increased eNOS protein levels up to 2.1-fold. Furthermore, we found an increased human eNOS promotor activity (up to 2-fold) in response to red wine polyphenols (18 hours, 100 to 600 g/mL), as demonstrated by a luciferase reporter gene assay. Conclusion-We

Resveratrol attenuates angiotensin II-induced interleukin-6 expression and perivascular fibrosis

“…This estimation may make the dose we used in this study clinically relevant. In addition, it has been reported that resveratrol at a lower concentration between 0.1 and 10 mmol l À1 has beneficial effects on the cardiovascular system, such as an inhibition of TNFa-induced NF-kB activation 36 and an increase in nitric oxide release, 37 suggesting that two glasses of red wine may also be beneficial. The level of resveratrol found in food varies greatly.…”

Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure

“…However, it is not known which specific polyphenolic compounds present in these foods are responsible for this beneficial effect. Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenol predominately found in red wine and grapes that has attracted much interest due to its cardioprotective potential shown in vivo (14)(15)(16). Resveratrol exists in cis-and trans-isomeric forms, but only trans-isomer is mainly present in wine (17), which can be found at highest concentration in grape skin in ranges between 50 and 400µg/g of fresh weight (18).…”

“…The purported cardiovascular benefits of resveratrol from experimental evidence include defence against ischaemic-reperfusion injury (21)(22)(23), suppression of platelet aggregation (16,24), enhanced antioxidant status (16,25) and increased NO bioavailability through enhanced endothelial NO synthase expression in cultured human endothelial cells (14)(15). Recently, the progression of endothelial dysfunction and vascular remodelling in rats with pulmonary and cardiac abnormalities were slowed after three weeks of daily resveratrol administration (25mg/kg) (26).…”

Resveratrol: A miraculous natural compound for diseases treatment

“…Several studies have been shown anti‐atherosclerotic, anti‐hypertensive, anti‐myocardial ischemia, anti‐stroke, and heart failure effects of it. Improvement of bioavailability of nitric oxide (NO) by RSV is one of the cardio‐protective mechanisms of this compound (Leikert et al., 2002). NO contributes to improved vasodilation and decreased platelet aggregation, leukocyte recruitment, and proliferation of smooth muscle cells, which are inhibitors of atherosclerosis formation and progression (Li & Förstermann, 2000).…”

“…One of protective mechanisms by RSV in cardiomyocytes is induction of autophagy via SIRT‐1 and AMPK activation and inhibition of fractalkine protein as inhibitor of RSV‐induced autophagy (Xuan et al., 2012). Both antioxidant activity and increasing of nitric oxide bioavailability actions of RSV are required to exert its anti‐ischemic effects (Leikert et al., 2002). Studying of cardiac stem cells demonstrated that RSV could potentiate the regeneration of infarcted myocardium (Gurusamy, Ray, Lekli, & Das, 2010).…”