[en] Dietary polyphenols have been widely studied for their health effects on different components of metabolic syndrome (MetS). In the present Thesis it was aimed to evaluate the beneficial effect of grape-seed polyphenols on endothelial dysfunction and hypertension (HTN) associated with MetS using cafeteria diet-fed rats as a model of MetS. Results showed that an acute dose of 375 mg/kg of a low-molecular grape seed extract (LM- GSPE) 6h after-administration was the most effective in lowering BP in this diet induced HTN model. This improvement was seen to be mediated by Sirtuin-1 (sirt-1) and blockage of the Renin-Angiotensin-Aldosterone System (RAAS) at reducing Ang I and in turns Ang II plasma levels, and as a consequence, improving the endothelial function. Otherwise, some of the principal polyphenol forms in LM-GSPE, such as (-)-epicatechin and (+)-catechin, also showed to act as modulators of endothelial dysfunction. Furthermore, it was demonstrated that at a low dose of 7mg/Kg of gallic acid, the main phenolic acid present in LM-GSPE, acutely reduced BP in spontaneously hypertensive rats, improving endothelial dysfunction by blockage of the RAAS as LM-GSPE. However, gallic acid in contrast to LM-GSPE increased plasma bradykinin levels and not involved Sirt-1 in its antihypertensive effect. Finally it was demonstrated that a chronic administration of grape-seed polyphenols attenuated the development of HTN and other cardiometabolic risk factors associated with MetS. Therefore, grape-seed polyphenols, including gallic acid, are proposed as good candidates to be used as as BP lowering agents in HTN associated with MetS.

[es] Los polifenoles presentes en la dieta se han estudiado extensivamente por sus efectos positivos sobre diferentes componentes del síndrome metabólico (MetS). En esta Tesis, se propuso evaluar el efecto positivo de los polifenoles de pepita de uva sobre la disfunción endotelial y la hipertensión (HTN) asociada al MetS, utilizando el modelo de dieta de cafetería como modelo de HTN asociada al MEtS. Los resultados mostraron que la una dosis aguda de 375 mg/Kg de un extracto de polifenoles de bajo peso molecular de pepita de uva (LM-GSPE) 6 horas post-administración fue la más efectiva para reducir la presión arterial en este modelo de HTN inducido por dieta. La implicación de la Sirtuina-1 (Sirt-1) y el bloqueo del Sistema Renina-Angiotensina-Aldosterona (SRAA), y por consiguiente, la mejora de la función endotelial, fueron demostrados. Por otro lado, se observó como algunos de los polifenoles más abundantes del LM-GSPE, como la (-)- epicatequina, la (+)-catequina o el ácido gálico, actuaron como moduladores de la función endotelial. Además se demostró que el ácido gálico, el ácido fenólico más abundante del extracto, a una dosis baja de 7 mg/Kg bajaba la presión arterial de manera aguda en ratas espontáneamente hipertensas, mejorando además la función endotelial mediante el bloqueo del SRAA, como sucedía con LM-GSPE. No obstante, y al contrario que el extracto, el ácido gálico aumentó la concentración de bradiquinina en plasma y además no se vio implicación de Sirt-1 en el efecto antihipertensivo. Finalmente se demostró que la administración crónica de polifenoles de pepita de uva atenúa la elevación de la presión arterial y el empeoramiento de otros factores de riesgo asociados al MetS. Por tanto, se proponen los polifenoles de pepita de uva, incluido el ácido gálico, como buenos agentes para el control de la presión arterial asociada al MetS.