Mechanism of the endothelium-dependent vasodilator effect of an alcohol-free extract obtained from a vinifera grape skin

• Published in: Pharmacological research Vol. 52; no. 4; pp. 321 - 327
• Main Authors: Madeira, Socorro Vanesca Frota, de Castro Resende, Angela, Ognibene, Dayane Teixeira, de Sousa, Marcelo Augusto Vieira, Soares de Moura, Roberto
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-10-2005
• Subjects: Alcohols; Animals; Endothelium-Dependent Relaxing Factors - pharmacology; Hyperpolarization; In Vitro Techniques; Male; Mesenteric; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; Nitric oxide; Norepinephrine - pharmacology; Plant Extracts - pharmacology; Rats; Rats, Wistar; Vasoconstrictor Agents - pharmacology; Vasodilation; Vitis - chemistry; Vitis labrusca; Vitis labrusca; Mesenteric; Nitric oxide; Vasodilation; Hyperpolarization
• ISSN: 1043-6618; 1096-1186
• 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 1
H-[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.