Ethanol withdrawal increases oxidative stress and reduces nitric oxide bioavailability in the vasculature of rats
Ethanol withdrawal increases oxidative stress and reduces nitric oxide bioavailability in the vasculature of rats
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DOI：
10.1016/j.alcohol.2014.12.001
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发表时间：
2015-02-01
期刊：
影响因子：
2.3
通讯作者：
Tirapelli, Carlos R.
中科院分区：
文献类型：
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作者：
Gonzaga, Natalia A.;Mecawi, Andre S.;Tirapelli, Carlos R.
我们分析了酒精戒断对血管和系统肾素-血管紧张素系统(RAS)和血管氧化应激的影响。雄性Wistar大鼠用3~9%(v/v)乙醇灌胃，连续21天。酒精戒断是由于突然停止治疗而引起的。实验于停用乙醇48h后进行。酒精戒断组大鼠对高架迷宫开放臂(EPM)的探索减少，血浆皮质酮水平升高。酒精戒断可显著升高血压和血浆血管紧张素II(Ang II)水平，但对血浆肾素活性(PRA)、血管紧张素转换酶(ACE)活性或血浆血管紧张素I(Ang I)水平无影响。各实验组血管Ang I、Ang II水平、血管紧张素转换酶活性/表达及AT(1)、AT(2)受体表达均无明显差异。血浆渗透压以及血浆钠、钾和血糖水平不受酒精戒断的影响。酒精戒断引起全身和血管氧化应激，表现为血浆硫代巴比妥酸反应物质(TBARS)水平升高和血管产生超氧阴离子。酒精戒断显著降低血浆和血管硝酸盐/亚硝酸盐水平。本研究的主要新发现是乙醇戒断可诱导血管氧化应激，并降低血管内一氧化氮(NO)水平。此外，我们的研究提供了新的证据，表明酒精戒断不会影响血管Ang II生成系统，同时刺激全身RAS。这些反应可能使个体更容易患上心血管疾病。(C)2015 Elsevier Inc.保留所有权利。
We analyzed the effects of ethanol withdrawal on the vascular and systemic renin-angiotensin system (RAS) and vascular oxidative stress. Male Wistar rats were treated with ethanol 3-9% (v/v) for a period of 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 h after ethanol discontinuation. Rats from the ethanol withdrawal group showed decreased exploration of the open arms of the elevated-plus maze (EPM) and increased plasma corticosterone levels. Ethanol withdrawal significantly increased systolic blood pressure and plasma angiotensin II (ANG II) levels without an effect on plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, or plasma angiotensin I (ANG I) levels. No differences in vascular ANG I, ANG II levels, and ACE activity/expression and AT(1) and AT(2) receptor expression were detected among the experimental groups. Plasma osmolality, as well as plasma sodium, potassium, and glucose levels were not affected by ethanol withdrawal. Ethanol withdrawal induced systemic and vascular oxidative stress, as evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels and the vascular generation of superoxide anion. Ethanol withdrawal significantly decreased plasma and vascular nitrate/nitrite levels. Major new findings of the present study are that ethanol withdrawal induces vascular oxidative stress and reduces nitric oxide (NO) levels in the vasculature. Additionally, our study provides novel evidence that ethanol withdrawal does not affect the vascular ANG II generating system while stimulating systemic RAS. These responses could predispose individuals to the development of cardiovascular diseases. (C) 2015 Elsevier Inc. All rights reserved.