Wine Polyphenols Improve Endothelial Function in Large Vessels of Female Spontaneously Hypertensive Rats

Abstract

Abstract-Red wine polyphenols (RWPs) have been reported to prevent hypertension and endothelial dysfunction.Several individual RWPs exert estrogenic effects. We analyzed the possible in vivo protective effects on blood pressure and endothelial function of RWPs in female spontaneously hypertensive rats (SHR) and its relationship with ovarian function. RWPs (40 mg/kg by gavage) were orally administered for 5 weeks. Ovariectomized rats showed both increased isoprostaglandin F 2␣ excretion and aortic superoxide production and reduced relaxant response to acetylcholine and contraction to the endothelial nitric oxide synthase (eNOS) inhibitor L-NAME measured in the aorta but similar blood pressure, as compared with sham-operated rats. Moreover, in ovariectomized rats aortic eNOS expression was unchanged, whereas caveolin-1, angiotensin II receptor (AT)-1, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22 phox and p47 phox expression was increased compared with sham-operated rats. In both ovariectomized and sham-operated SHR, RWPs reduced systolic blood pressure, urinary isoprostaglandin F 2␣ excretion, and aortic O 2 Ϫ production, improving the endothelium-dependent relaxant response to acetylcholine in SHR. These changes were associated with unchanged aortic eNOS expression, whereas caveolin-1 was increased and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22 phox and p47 phox expression was reduced. RWPs had no effect on the AT-1 overexpression found in ovariectomized animals. All these results suggest that a chronic treatment with RWPs reduces hypertension and vascular dysfunction through reduction in vascular oxidative stress in female SHR in a manner independent of the ovarian function. Key Words: red wine polyphenols Ⅲ spontaneously hypertensive rat Ⅲ endothelial dysfunction Ⅲ NADPH oxidase Ⅲ ovariectomy T he incidence of cardiovascular diseases among premenopausal women is lower than age-matched, men but it rises markedly after menopause. Blood pressure is also higher in men than in women at similar ages, 1 and this difference is also reduced or even inverted after menopause. The loss of estrogens has been suggested as a major risk factor for postmenopausal hypertension. Estrogen receptor (ER) subtypes ER␣ and ER␤ are expressed in endothelial and smooth muscle cells. [2][3][4][5] Estrogens increase endothelial-derived NO, modulate the local tissue reninangiotensin system, and show antioxidant effects. [3][4][5][6][7][8][9][10] Long-term estrogen treatment improves endothelial dysfunction, through upregulation of endothelial nitric oxide synthase (eNOS), 11,12 posttranslational modulation of eNOS activity, 13 or nongenomic effects, including activation of NO synthesis. 14,15 However, despite the positive effects on vascular function found in cell culture, 12,14 ex vivo 15 and in vivo animal 16 -18 and short-term human 7,19 -21 studies, estrogen replacement therapy has failed to protect from cardiovascular diseases in large scale randomized controlled ...

Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients

“…48 Moreover, our results clearly showed that red wine and de-alcoholized red wine significantly decreased SBP and DBP in the MetS patients and these results agree with those of other studies, which have reported that polyphenols reduce elevated blood pressure. 49 Interestingly, polyphenols and polyphenols plus ethanol significantly reduced the blood glucose levels in the MetS patients compared to baseline, possibly due to the shift in the gut microbiota to a higher proportion of Gram-positive relative to Gram-negative bacteria produced by the presence of polyphenols. It has been found that type 2 diabetes mellitus might be associated with the dominance of Gram-negative bacteria in the gut.…”

Inhibitory effect of catechin-related compounds on renin activity

“…Although many ACE inhibitors derived from foodstuffs have been identified in the past (7), only a few reports on natural renin inhibitors were available (6,11,20,21). Studies have supported that polyphenol-containing materials such as black and green tea (14), red wine (12), cocoa extract (5,17) and azuki bean seed coats (13) could reduce blood pressure in several experimental hypertensive models. The mechanisms underlying this effect were proposed to be attributable to vasodilator action, the attenuation of vascular oxidative stress and inflammation, and the ability to reduce arginase-2 activity (18), as well as the inhibitory effect against ACE (1,3).…”

An ethanolic extract of Lindera obtusiloba stems causes NO-mediated endothelium-dependent relaxations in rat aortic rings and prevents angiotensin II-induced hypertension and endothelial dysfunction in rats

“…Polyphenols might protect the cardiovascular system by a variety of actions, including their ability to improve the lipid profile; dilate blood vessels by stimulating the endothelial formation of NO, and also in some blood vessels EDHF, and by their antioxidant properties, which will prevent the degradation of NO by superoxide anions (Sarr et al 2006;Stoclet et al 2004;Frankel et al 1993;Fitzpatrick et al 2000;Madeira et al 2009;Mann et al 2007;Ndiaye et al 2005). In addition, polyphenol-rich sources such as a red wine extract have been shown to reduce systolic blood pressure and to improve endothelial dysfunction in several experimental models of hypertension (Sarr et al 2006;Lopez-Sepulveda et al 2008;de Moura et al 2004;Bernatova et al 2002;Schini-Kerth et al 2010). Altogether, these findings support the view that polyphenol-rich natural products may protect the cardiovascular system, in part, by improving the endothelial function and, hence, retarding the development of cardiovascular diseases.…”