Mechanism of the Endothelium-Dependent Relaxation

Evoked by a Grape Seed Extract

Indika EDIRISINGHE, Britt BURTON-FREEMAN and C. Tissa KAPPAGODA

Department of Internal Medicine, University of California Davis, Davis, CA 95616, U.S.A., and Department of Nutrition, University of California Davis, Davis, CA 95616, U.S.A.

Abstract

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.

Effect of Grape Seed Extract on Blood Pressure

in Subjects with the Metabolic Syndrome

Brahmesh Sivaprakasapillaia, Indika Edirisingheb, Jody Randolphc,Francene Steinbergc, Tissa Kappagodaa

Department of Internal Medicine, University of California Davis, Davis, CA 95616, USA

National Center for Food Safety and Technology, Illinois Institute of Technology, Moffet Campus, Summit-Argo, IL 60501, USA

Department of Nutrition, University of California Davis, Davis, CA 95616, USA

Received 21 November 2008; accepted 29 May 2009

Abstract

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.

References

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