Direct effect of ethanol on human vascular function.
Direct effect of ethanol on human vascular function.
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乙醇对人体血管功能的直接影响。
DOI：
10.1152/ajpheart.01207.2003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Creager,MarkA
中科院分区：
文献类型：
--
作者：
Tawakol,Ahmed;Omland,Torbjørn;Creager,MarkA
流行病学研究表明，适量饮酒可降低心血管死亡率。细胞和动物数据表明，乙醇对血管内皮具有有益作用，并增加一氧化氮的生物利用度。本研究的目的是评估乙醇对健康人类受试者内皮依赖性、一氧化氮介导的血管舒张的影响。健康受试者在动脉内输注乙酰甲胆碱（0.3、1.0、3.0 和 10.0 mcg/min，n= 9）、硝普钠（0.3、1.0、3.0 和 10.0 mcg/min，n= 9）或在同时动脉内输注乙醇（10% 乙醇溶于 5% 葡萄糖）之前和期间，维拉帕米（10、30、100 和 300 mcg/min，n= 8）。此外，还进行了时间控制实验，在载体输注期间测量了两次乙酰甲胆碱剂量反应曲线（n=5）。乙醇输注期间，平均前臂和全身酒精水平分别为 227 ± 30 和 6 ± 0 mg/dl。单独输注乙醇可降低 FBF（2.5 ± 0.1 至 1.9 ± 0.1 ml·dl−1·min−1，P< 0.05）。尽管最初有血管收缩作用，但乙醇增强了乙酰甲胆碱、硝普钠和维拉帕米的 FBF 剂量反应曲线（方差分析显示，每种药物的 P < 0.01）。为了确定这种增强的 FBF 反应是否与剪切应力诱导的一氧化氮释放有关，在静息时和维拉帕米诱导的血管舒张期间测量乙醇和 NG-硝基-l-精氨酸 (l-NAME;n= 8) 的混合期间的 FBF。添加l-NAME并不会阻止乙醇增强维拉帕米诱导的血管舒张的能力。乙醇具有复杂的直接血管作用，包括基础血管收缩以及内皮依赖性和非依赖性血管舒张的增强。这些效应似乎都不是由一氧化氮生物利用度的增加介导的，因此对临床前模型的发现存在争议。
Epidemiological studies indicate that moderate ethanol consumption reduces cardiovascular mortality. Cellular and animal data suggest that ethanol confers beneficial effects on the vascular endothelium and increases the bioavailability of nitric oxide. The purpose of this study was to assess the effect of ethanol on endothelium-dependent, nitric oxide-mediated vasodilation in healthy human subjects. Forearm blood flow (FBF) was determined by venous occlusion plethysmography in healthy human subjects during intra-arterial infusions of either methacholine (0.3, 1.0, 3.0, and 10.0 mcg/min,n= 9), nitroprusside (0.3, 1.0, 3.0, and 10.0 mcg/min,n= 9), or verapamil (10, 30, 100, and 300 mcg/min,n= 8) before and during the concomitant intra-arterial infusions of ethanol (10% ethanol in 5% dextrose). Additionally, a time control experiment was conducted, during which the methacholine dose-response curve was measured twice during vehicle infusions (n= 5). During ethanol infusion, mean forearm and systemic alcohol levels were 227 ± 30 and 6 ± 0 mg/dl, respectively. Ethanol infusion alone reduced FBF (2.5 ± 0.1 to 1.9 ± 0.1 ml·dl−1·min−1,P< 0.05). Despite initial vasoconstriction, ethanol augmented the FBF dose-response curves to methacholine, nitroprusside, and verapamil (P< 0.01 by ANOVA for each). To determine whether this augmented FBF response was related to shear-stress-induced release of nitric oxide, FBF was measured during the coinfusion of ethanol andNG-nitro-l-arginine (l-NAME;n= 8) at rest and during verapamil-induced vasodilation. The addition ofl-NAME did not block the ability of ethanol to augment verapamil-induced vasodilation. Ethanol has complex direct vascular effects, which include basal vasoconstriction as well as potentiation of both endothelium-dependent and -independent vasodilation. None of these effects appear to be mediated by an increase in nitric oxide bioavailability, thus disputing findings from preclinical models.