This study was undertaken to determine whether grape seed extracts (GSE) that contain powerful vasodilator phenolic compounds lower blood pressure in subjects with the metabolic syndrome. The subjects were randomized into 3 groups—(a) placebo, (b) 150 mg GSE per day, and (c) 300 mg GSE per day—and treated for 4 weeks. Serum lipids and blood glucose were measured at the beginning of the study and at the end. Blood pressure was recorded using an ambulatory monitoring device at the start of the treatment period and at the end. Both the systolic and diastolic blood pressures were lowered after treatment with GSE as compared with placebo. There were no significant changes in serum lipids or blood glucose values. These findings suggest that GSE could be used as a nutraceutical in a lifestyle modification program for patients with the metabolic syndrome.

GSEs (grape seed extracts) which contain polyphenolic compounds cause an endotheliumdependent 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 ?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 (NG-nitro-Larginine 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.

Oral administration of grape seed extract (Meganatural-BP Patent pending) (GSE) lowered the blood pressure in human subjects with the metabolic syndrome. We tested the hypothesis that GSE caused an endothelium dependent relaxation (EDR) in aortic rings from New Zealand White rabbits. The rings were suspended in organ baths containing oxygenated Krebs buffer at 37C. EDR evoked by acetylcholine (Ac) and GSE were measured after pre-contracting the rings with 10-5 M noradrenalin. The tissues were also tested after removing the endothelium and after incubation with L-NAME, Wotmannin (Wot) and LY 294002 (LY) and SU5416 (SU) to examine the mechanism involved in the relaxation. We also investigated the phosphorylation of e-NOS (Ser-1177) by GSE in- vitro in HUVECs. Relaxation to GSE was abolished in de-endothelialized and L-NAME treated tissues. The EDR was inhibited by PI3 kinase inhibitors (Wot and Ly) but not by SU (VEGFR2 inhibitor). Involvement of e-NOS was confirmed by phosphorylation of e-NOS (Ser-1177) in HUVECs after exposure to GSE. It is concluded that GSE caused EDR by activation of the AKT/PI3 kinase pathway via a mechanism which does not involve VEGFR2.

This study was undertaken to determine whether grape see extracts (GSE) which contain powerful vasodilator phenolic compounds lower blood pressure (BP) in subjects with pre-hypertension. The subjects were randomized into a placebo or an experimental group (GSE at a dose of 300 mg/day) and treated for 8 weeks. Serum lipids and blood glucose were measured at the beginning of the study and at the end. BP was recorded using an ambulatory monitoring device at the start of the treatment period and at the end. Both the systolic and diastolic blood pressure were lower after treatment with GSE as compared with placebo. There were no significant changes in serum lipids or blood glucose values. These findings suggest that GSE could be used as a nutraceutical in a lifestyle modification program for patients with pre-hypertension.