Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats.
Chronic ethanol ingestion induces aortic inflammation/oxidative endothelial injury and hypertension in rats.
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DOI：
10.1177/0960327110384520
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发表时间：
2011-08
影响因子：
2.8
通讯作者：
Lalla J
中科院分区：
文献类型：
--
作者：
Husain K;Ferder L;Ansari RA;Lalla J
本研究旨在探讨慢性酒精性炎症导致的血管内皮损伤与血压升高的关系。将雄性Fisher大鼠分为两组，每组6只：(1)对照组(5%蔗糖，口服)，连续12周；(2)20%乙醇(4g·kg·−-1，口服)，连续12周。每周记录平均动脉压。12周后用戊巴比妥钠麻醉，分离胸主动脉，检测主动脉反应性、炎症介质、氧化/抗氧化酶蛋白表达和内皮一氧化氮生成系统。结果显示，酒精摄入12周后，平均血压显著升高。与对照组相比，酒精组血压升高与主动脉炎症(肿瘤坏死因子-α、一氧化氮合酶、环氧合酶-2和单核细胞趋化蛋白-1蛋白表达)增加和血管紧张素II水平升高有关。与对照组相比，酒精处理组大鼠主动脉NADPH氧化酶活性显著降低，膜和胞浆亚基p22Phox和p47Phox表达显著增加，而一氧化氮(NO)、内皮型一氧化氮合酶(ENOS)、血管内皮生长因子-A(VEGFA)和CuZn-SOD活性及蛋白表达显著降低。与对照组相比，乙醇处理组大鼠的主动脉中乙酰胆碱介导的血管松弛反应受到抑制。综上所述，慢性乙醇诱导的血压升高与大鼠主动脉炎症加重、血管紧张素II水平升高、NADPH氧化酶诱导引起内皮损伤、CuZn-SOD耗竭、内皮NO生成系统下调和血管松弛受损有关。
The study aim was to investigate the relationship of chronic ethanol-induced inflammation leading to vascular endothelial injury and elevation of blood pressure (BP) in a rat model. Male Fisher rats were divided into two groups of six animals each and treated as follows: (1) Control (5% sucrose, orally) daily for 12 weeks and (2) 20% ethanol (4 g kg −1, orally) daily for 12 weeks. The mean arterial blood pressure was recorded every week. The animals were anesthetized with pentobarbital after 12 weeks; thoracic aorta were isolated and analyzed for aortic reactivity response, inflammatory mediators, oxidant/antioxidant enzyme protein expression and endothelial nitric oxide-generating system. The results show that the mean BP was significantly elevated 12 weeks after ethanol ingestion. The increased BP was related to increased aortic inflammation (tumor necrosis factor [TNF]-α; nitric oxide synthase [iNOS], COX-2 and MCP-1 protein expression) and elevated angiotensin II levels in alcohol-treated group compared to control. Aortic Nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity, membrane and cytosolic subunits p22phox and p47phox expression and Mn-SOD activity and protein expression significantly increased, whereas nitric oxide (NO), endothelial NO synthase (eNOS), vascular endothelial growth factor (VEGF)-A and CuZn-SOD activity and protein expression significantly decreased in alcohol-treated group compared to control. The acetylcholine-mediated vasorelaxation response was depressed in the aorta of ethanol-treated rats compared to control. In conclusion, chronic ethanol-induced elevation in BP is related to increased aortic inflammation, elevated angiotensin II levels, induction of NADPH oxidase causing endothelial injury, depletion of CuZn-SOD, down-regulation of endothelial NO generating system and impaired vascular relaxation in rats.