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标题：Grape Extract from Chardonnay Seeds Restores Deoxycorticosterone Acetate–Salt-Induced Endothelial Dysfunction and Hypertension in Rats
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作者：Akihiro Sato ; Satoshi Nishioka ; Mika Kiuchi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2020
卷号：43
期号：1
页码：59-67
DOI：10.1248/bpb.b19-00540
出版社：The Pharmaceutical Society of Japan
摘要：Grape extract (GE), which contains various polyphenolic compounds, exerts protective effects against lifestyle-related diseases, such as diabetes and hypertension. We pharmacologically investigated whether dietary supplements with an extract from Chardonnay exerted antihypertensive effects in deoxycorticosterone acetate (DOCA)–salt-induced hypertensive rats. GE increased nitric oxide (NO) production by activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in cultured endothelial cells and induced vasorelaxation in the aorta and mesenteric artery via the same pathway. The development and progression of hypertension by the DOCA–salt treatment was significantly inhibited in GE-fed rats. Reduced vasoreactive responses to acetylcholine in the aorta of DOCA–salt rats were significantly ameliorated by the GE diet. Dietary GE supplements slightly diminished vascular superoxide anion production induced by the DOCA–salt treatment. On the other hand, dietary GE supplements had no effect on the progression of hypertension in rats in which NO synthase was pharmacologically and chronically suppressed. In addition, the oral administration of GE for 5 d in healthy rats enhanced endothelial NO synthase (eNOS) gene expression and vascular reactivity to acetylcholine in the aorta. Thus, GE has endothelium-dependent vasorelaxant properties that are mediated by the activation of endothelial NO synthase via the PI3K/Akt pathway, and this mechanism is conducive to the antihypertensive effects of GE observed in DOCA–salt-treated rats.
关键词：grape extract;nitric oxide;deoxycorticosterone acetate (DOCA);salt;antihypertensive effect