Chronic alcohol-induced oxidative endothelial injury relates to angiotensin II levels in the rat
Chronic alcohol-induced oxidative endothelial injury relates to angiotensin II levels in the rat
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DOI：
10.1007/s11010-007-9583-6
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Lalla, Jainarine
中科院分区：
文献类型：
--
作者：
Husain, Kazim;Vazquez, Manuel;Lalla, Jainarine
长期饮酒与心血管损伤包括高血压之间的联系是众所周知的。然而，与酒精诱导的血压（BP）升高有关的分子介质仍然难以捉摸。本研究的目的是探讨慢性乙醇诱导的内皮损伤和血压升高与血管紧张素II水平的关系。将雄性Fisher大鼠分为两组，每组7只，并按如下方法处理：（1）对照组（5%蔗糖，口服），每天一次，持续12周;（2）乙醇组（4 g/kg，口服），每天一次，持续12周。每周记录血压（收缩压、舒张压和平均血压）。12周后，用戊巴比妥麻醉动物;分离血液和胸主动脉，并分析主动脉反应性反应、血管紧张素II水平和氧化性内皮损伤。结果表明，收缩压，舒张压和平均血压显着升高后12周的乙醇摄入。与对照组相比，酒精治疗组血压升高与血浆和主动脉血管紧张素II水平升高有关。酒精组主动脉NADPH氧化酶活性、氧化型谷胱甘肽/还原型谷胱甘肽比值（GSSG/GSH）和脂质过氧化水平显著升高，而一氧化氮（NO）、内皮型一氧化氮合酶（eNOS）和血管内皮生长因子（VEGF）蛋白表达均显著降低。苯肾上腺素介导的血管收缩反应没有改变，而乙酰胆碱介导的血管舒张反应被抑制在主动脉中的乙醇处理的大鼠相比，控制。它的结论是，慢性乙醇摄入诱导高血压，这是与升高的组织血管紧张素II水平，激活NADPH氧化酶活性引起内皮损伤，内皮NO生成系统的耗尽，和受损的血管舒张大鼠。
The link between chronic alcohol consumption and cardiovascular injury including hypertension is well known. However, molecular mediators implicated with alcohol-induced elevation in blood pressure (BP) remain elusive. The aim of this study was to investigate the relationship of chronic ethanol-induced endothelial injury and elevation in BP with angiotensin II levels in rats. Male Fisher rats were divided into two groups of seven animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) ethanol (4 g kg(-1), orally) daily for 12 weeks. The BP (systolic, diastolic, and mean) was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; blood and thoracic aorta were isolated and analyzed for aortic reactivity response, angiotensin II levels, and oxidative endothelial injury. The results show that the systolic, diastolic, and mean BP were significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to elevated angiotensin II levels in the plasma and aorta of alcohol treated group compared to control. The aortic NADPH oxidase activity, ratio of oxidized to reduced glutathione (GSSG/GSH) and lipid peroxidation significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), and vascular endothelial growth factor (VEGF) protein expressions were depressed in alcohol group compared to control. The phenylephrine-mediated vasoconstriction response was not altered, while acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol treated rats compared to control. It is concluded that chronic ethanol ingestion induces hypertension which is correlated with elevated tissue angiotensin II levels, activation of NADPH oxidase activity causing endothelial injury, depletion of endothelial NO generating system, and impaired vascular relaxation in rats.