Dietary (-)-epicatechin improves hypertension in associataion with modifications in NOX and eNOS vascular expression in a rat model of metabolic sydrome

LITTERIO MC; VAZQUEZ PRIETO MA; ADAMO AM; OTEIZA PI; FRAGA CG; GALLEANO M

Paris

Congreso; 5ème Symposium Nutrition, Biologie de l`Oxigène et Médicine-Paris; 2013

Metabolic syndrome (MS) is defined as a multiplex risk factor for cardiovascular disease (CVD). Flavonoids have shown to be efficient decreasing blood pressure (BP) in human and animal models of MS. The effects of flavonoids on hypertension appear to be mechanistically related to nitric oxide (NO) bioavailability, partially regulated through the activation of nitric oxide synthase (NOS) and/or the inhibition of NADPH oxidase (NOX). The aim of this work was to evaluate the antihypertensive effect of dietary (-)-epicatechin (EC), a relevant component of cocoa, in fructose-fed rats, a model of MS. Male Sprague-Dawley rats were divided into 3 groups and administered during 8 weeks with fructose in the drinking water (10% w/v) in the absence or the presence of EC supplementation in the diet (20 mg/Kg BW/day) as follows: Control group (C), Fructose group (F) and Fructose + EC group (FEC) according to the beverage and diet provided. BP was measured by tail-cuff plethysmography at the end of the experimental period. F group showed a singnificant increase in BP, which was completely avoided by the presence of EC in the diet. Superoxide anion role was examined through the expression of p47phox (NOX subunit) by western blot in aorta homogenates. F group showed a 2.1-fold increase in p47phox expression, respect to C and FEC groups. Additionally, the localization of this protein across the aortic wall was evaluated by immunohistochemistry and the modifications in p47phox were produced essentially in the intima and adventitia layers. F group showed a significantly increased fluorescent signal for p47phox respect to C group, and this enhancement was absent in FEC group. NOX4 and p22phox (NOX subunits) expressions in aorta were also significantly augmented by fructose overload, respect to C and FEC groups. In addition, expression of endothelial NOS (eNOS) in aorta homogenates was measured by western blot. Results showed a higher eNOS expression in F group respect to C and FEC groups, and this eNOS over expression could be explained as a compensatory mechanism for the diminished NO availability generated by an excessive superoxide anion production in this model. As a conclusion, the increase in BP associated with fructose overload treatment was not present in FEC group. This effect could be related to the attenuation in superoxide anion production through the inhibition of NOX expression and consequent increasing NO bioavailability.