Madeira Socorro Vanesca Frota, de Castro Resende Angela, Ognibene Dayane Teixeira, de Sousa Marcelo Augusto Vieira, Soares de Moura Roberto
Department of Pharmacology, IBRAG-CB State University of Rio de Janeiro, Av. 28 de setembro, 87, CEP 20551-030 Rio de Janeiro, Brazil.
Pharmacol Res. 2005 Oct;52(4):321-7. doi: 10.1016/j.phrs.2005.05.005.
An alcohol-free grape-skin extract (GSE) obtained from skins of Vitis labrusca has significant anti-hypertensive, antioxidant and vasodilator effects. According to our previous results, the vasodilator effect of GSE in the isolated mesenteric vascular bed (MVB) of the rat is dependent on endothelium and partially dependent on nitric oxide (NO). In the MVB of the rat pre-contracted with norepinephrine (NE), bolus injections of GSE induced a long-lasting dose-dependent vasodilation that is significantly reduced after the treatment with 1H-[1,2,3] oxadiazolo [4,4-a] quinoxalin-1-one (ODQ). Additionally, in vessels pre-contracted with norepinephrine and depolarized with KCl (25 mM) or treated with Ca(2+)-dependent K(+)-channel blockers charybdotoxin (ChTx) plus apamin, the vasodilator effect of GSE was significantly reduced and almost abolished by ChTx plus apamin plus L-NAME. However, the vasodilator effect of GSE was unaffected by D-Arg[Hyp(3),Thi(5),D-Tic(7),Oic(8)]bradykinin (HOE-140), atropine, yohimbine, pyrilamine and 4-aminopyridine (4-AP). The vasoconstriction response elicited by bolus injection of KCl was not affected by GSE, whereas the vasoconstrictor response induced by NE was dose-dependently and completed inhibited by GSE in the presence but not in the absence of endothelium. However, NE-induced vasoconstriction in calcium-free condition or without endothelium was not reduced by GSE. The present results demonstrate that GSE induces a vasodilator effect in the rat MVB, which is dependent on NO in combination with endothelium-derived hyperpolarizing factor (EDHF). Additionally, our results indicated that extracellular Ca(2+) has an important role on the endothelium-dependent vasodilator effect induced by GSE.
从美洲葡萄皮中提取的无酒精葡萄皮提取物（GSE）具有显著的抗高血压、抗氧化和血管舒张作用。根据我们之前的研究结果，GSE在大鼠离体肠系膜血管床（MVB）中的血管舒张作用依赖于内皮细胞，且部分依赖于一氧化氮（NO）。在预先用去甲肾上腺素（NE）收缩的大鼠MVB中，静脉注射GSE可诱导持久的剂量依赖性血管舒张，在用1H-[1,2,3]恶二唑并[4,4-a]喹喔啉-1-酮（ODQ）处理后，这种血管舒张作用显著减弱。此外，在预先用去甲肾上腺素收缩并经氯化钾（25 mM）去极化或用钙依赖性钾通道阻滞剂蝎毒素（ChTx）加蜂毒明肽处理的血管中，GSE的血管舒张作用显著减弱，ChTx加蜂毒明肽加左旋精氨酸甲酯（L-NAME）几乎可将其完全消除。然而，GSE的血管舒张作用不受D-精氨酸[Hyp(3),Thi(5),D-Tic(7),Oic(8)]缓激肽（HOE-140）、阿托品、育亨宾、吡拉明和4-氨基吡啶（4-AP）的影响。静脉注射氯化钾引起的血管收缩反应不受GSE影响，而在有内皮细胞存在但无内皮细胞时，GSE可剂量依赖性地完全抑制NE诱导的血管收缩反应。然而，在无钙条件下或无内皮细胞时，NE诱导的血管收缩不受GSE影响。目前的研究结果表明，GSE在大鼠MVB中诱导血管舒张作用，这依赖于NO与内皮衍生超极化因子（EDHF）的共同作用。此外，我们的结果表明，细胞外钙（2+）在GSE诱导的内皮依赖性血管舒张作用中起重要作用。
