Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract

Abstract

GSEs (grape seed extracts) which contain polyphenolic compounds cause an endothelium-dependent relaxation of blood vessels. The aim of the present study was to examine the mechanisms involved in this response. A well-characterized GSE was applied to rabbit aortic rings suspended in organ baths containing Krebs-Henseleit buffer maintained at 37 degrees C. In aortic rings pre-contacted with noradrenaline (norepinephrine), the extract produced a dose-dependent relaxation. The maximum relaxations elicited by the extract (71.9+/-1.0%) were similar to those elicited by acetylcholine (64.2+/-1.5%) (n=12 for each). As expected, the relaxations were abolished by removal of the endothelium and by prior incubation with L-NAME (N(G)-nitro-L-arginine methyl ester), confirming the essential role of eNOS (endothelial NO synthase) in the response. The responses to the GSE were also abolished by incubation with wortmannin and LY294002, which are inhibitors of PI3K (phosphoinositide 3-kinase). These compounds had no effect on the responses to acetylcholine. Using immunoblotting, we also demonstrated that the GSE induced the phosphorylation of both Akt and eNOS in HUVECs (human umbilical vein endothelial cells). Finally, the extract was modified by methylation of the hydroxy groups in the polyphenolic groups and was applied to the aortic rings. The modified extract failed to cause a relaxation. Taken together, these findings suggest that the endothelium-dependent relaxation induced by the GSE was mediated by activation of the PI3K/Akt signalling pathway through a redox-sensitive mechanism, resulting in phosphorylation of eNOS.

Endothelium-dependent vasodilator and antioxidant properties of a novel enzymatic extract of grape pomace from wine industrial waste

“…Thus, NO is involved in the in vitro vasodilator effects of red wine polyphenolic compounds (Andriambeloson, Kleschyov, Muller, Beretz, Stoclet & Andriantsitohaina, 1997;Andriambeloson, Stoclet, & Andriantsitohaina, 1999), grape seed (Edirisinghe et al, 2008;Fitzpatrick, Bing, Maggi, Fleming & O'Malley, 2002;Fitzpatrick, Fleming, Bing, Maggi & O'Malley, 2000) and grape skin extracts (Madeira et al, 2009). Regarding to grape pomace extracts, studies about their vascular effects have not been reported until now and studies concerning grape pomace extracts are limited to antioxidant (Chidambara Murthy, Singh, & Jayaprakasha, 2002) and anti-inflammatory properties associated with obesity and insulin resistance (Hogan, Canning, Sun, Sun & Zhou, 2010a;Yunoki et al, 2008).…”

“…In the recent years, an increasing attention has been focused on the positive effects of grape seeds extracts (Edirisinghe, Burton-Freeman, & Kappagoda, 2008) and grape skin extracts (Madeira et al, 2009) on the vascular function in isolated arteries. Grape seed extracts have also shown anti-angiogenic properties in endothelial cells (Lu, Zhang, Chen, & Wen, 2009) and protection against atherosclerosis biomarkers in vitro (Vinson, Mandarano, Shuta, Bagchi, & Bagchi, 2002).…”

Evidence for a protective effect of polyphenols-containing foods on cardiovascular health: an update for clinicians

“…Individually, GSE and quercetin were reported to cause an endothelium-dependent relaxation of blood vessels both in animals [Edirisinghe et al 2008;Khoo et al 2010] and in humans [Clifton, 2004;Loke et al 2008]. However, when combined, quercetin appeared to nullify the positive effect of GSE on endothelial function in high-risk subjects [Clifton, 2004].…”

The role of nutrition and nutraceutical supplements in the treatment of hypertension

“…Significant reduction in BP of 11/8 mmHg (p < 0.05) were seen in another dose response study with 150 to 300 mg/d of GSE over 4 wk [306] . GSE has high phenolic content which activates the PI3K/Akt signaling pathway that phosphorylates eNOS and increases NO [306,307] .…”