Critique 030: Young rats given red wine polyphenols show less deterioration in endothelial function with ageing. 30 January 2011

Dal-Ros S, Zoll J, Lang AL, Auger C, Keller N, Bronner C, Geny B, Schini-Kerth VB.   Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: Role of NADPH oxidase.  Biochem Biophys Res Commun 2011;404:743-749.

Authors’ Abstract

Aging is associated with oxidative stress-mediated endothelial dysfunction and decline in physical performance, which promote cardiovascular diseases.  This study examined whether chronic intake of red wine polyphenols (RWPs), a rich source of natural antioxidants, prevents aging-related impairment of vascular function and physical exercise capacity.  Vascular reactivity from 12, 20 and 40 week-old rats was assessed in organ chambers.  Rats received from week 16 to 40 either solvent, RWPs or the antioxidant and NADPH oxidase inhibitor, apocynin.  Aging was associated with blunted endothelium-dependent relaxations, oxidative stress (dihydroethidine staining), and an upregulation of eNOS, arginase I, NADPH oxidase p22phox and nox1 subunits, and AT1 and AT2 receptors (assessed by immunohistochemistry) in the mesenteric artery.  RWPs and apocynin improved the endothelial dysfunction, normalized oxidative stress and the expression of the different proteins.  RWPs also improved aging-related decline in physical exercise.  Thus, intake of RWPs protects against aging-induced endothelial dysfunction and decline in physical performance.  These effects likely involve the ability of RWPs to normalize oxidative stress and the expression of proteins involved in the formation of NO and the angiotensin II pathwauy.

Forum Comments

Forum members thought that this was an excellent paper, as it begins to delve into mechanisms by which polyphenols improve health.  A mechanism is addressed and results are consistent with the working hypothesis of a specific interaction between polyphenols and peculiar enzymes. There is a satisfying agreement between basic mechanisms and pathophysiology.

Other Forum members stated that the novel finding in the present study is that regular intake of red wine polyphenols by young rats prevented aging-induced endothelial dysfunction as indicated by improved NO- and EDHF-mediated relaxations in the old mesenteric artery.  It is unfortunate that the authors do not study why this is happening.  They state that “RWPs prevented the aging-induced upregulation of NADPH oxidase subunits p22phox and nox1”.  These enzymes are responsible for the formation of superoxide and hence the increase in free radicals.  What is important to stress is that red wine contains apocynin-like compounds.  Indeed, previous studies have shown that the presence of an aromatic vicinal hydroxy-methoxy arrangement is highly effective in defining NADPH oxidase inhibition.1,2  Red wine polyphenols may therefore outcompete apocynin with respect to its inhibitory potency.  The combined inhibition of NADPH oxidase and the scavenging of reactive oxygen species by phenolic metabolites would be expected to affect local NO concentrations without influencing global endothelial nitric oxide production.

 Some scientists believe that interventions to improve endothelial function (such as the consumption of red wine or other sources of polyphenols) should begin earlier in life to slow down the endothelial dysfunction that occurs with ageing.  An intervention study from Chile showed that younger people show significant improvement in measures of endothelial function from 10 days of red wine intake.3  Leighton has stated that since endothelial function is such a key process involved in the development of cardiovascular disease, such findings suggest that earlier intake of wine may be beneficial.4  Most people consider that any advice regarding the consumption of wine should be limited to older people.  The present study suggests that intervention earlier in life, at least in rats, may have benefits.

 References from Forum Review
1.  Schewe T, Steffen Y, Sies H.  How do dietary flavanols improve vascular function?  A position paper.  Arch Biochem Biophys 2008;476:102-106.

2.  Steffen Y, Schewe T, Sies H. (-)-Epicatechin elevates nitric oxide in endothelial cells via inhibition of NADPH oxidase.  Biochem Biophys Res Commun 2007;359:828-833.

3.  Cuevas AM, Guasch V, Castillo O, Irribarra V, Mizon C, San Martin A, Strobel P, Perez D, Germain AM, Leighton F.  A high-fat diet induces and red wine counteracts endothelial dysfunction in human volunteers.  Lipids 2000;35:143–148.

4.  Leighton F, quoted in Panel Discussion I: Does alcohol consumption prevent cardiovascular disease? Ann Epidemiol 2007;17:S37–S39.

Forum Summary:  A key factor in the ageing process is a decrease in endothelial function, which is associated with the development of cardiovascular disease and other diseases of ageing.  This study in rats examined whether red wine polyphenols (RWPs) prevent aging-related impairment of vascular function.  While ageing was associated with decreases in endothelial function, rats given RWPs from a young age showed better endothelial function and less oxidative stress.  The authors hypothesize that these effects likely involve the ability of RWPs to normalize oxidative stress and the expression of proteins involved in the formation of NO and the angiotensin II pathway. 

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Contributions to this critique by the International Scientific Forum on Alcohol Research were made by the following members:

Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy

David Vauzour, PhD, Dept. of Food and Nutritional Sciences, The University of Reading, UK

R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

Federico Leighton, MD, Laboratorio de Nutricion Molecular, Facultad de Ciencias Biologicas, Universidad Catolica de Chile, Santiago, Chile