Husain Kazim, Vazquez-Ortiz Manuel, Lalla Jainarine
Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, PR 00732, USA.
Hum Exp Toxicol. 2007 May;26(5):427-34. doi: 10.1177/0960327106072993.
The aim of this study was to investigate the relationship between chronic ethanol-induced increase in blood pressure (BP) and alterations in the aortic nitric oxide (NO) and the antioxidant systems in rats. Male Fisher rats (200-250 g) 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, orally) daily for 12 weeks. The BP (systolic, diastolic and mean) was recorded every week through tail-cuff method. The animals were sacrificed 12 weeks after treatments and thoracic aorta was collected and analysed. The results show that systolic, diastolic and mean BP was significantly elevated 12 weeks after ethanol ingestion in rats compared to control. The endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expressions were down-regulated (50-55% of control) leading to depletion of aortic NO levels (69% of control) in ethanol treated rats compared to control. The ratio of reduced to oxidized glutathione (GSH/GSSG) was significantly depleted (58% of control) in the aorta of ethanol-treated rats compared to control. The decrease in aortic GSH/GSSG ratio was good correlated with increase in BP (r = 0.69). The antioxidant enzymes: copper/zinc-superoxide dismutase (CuZn-SOD) and manganese (Mn)-SOD, catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly depressed (36-53% of control) in the aorta of ethanol-treated rats compared to control. The study concluded that chronic ethanol ingestion induces hypertension which relates to the vascular endothelial dysfunction on account of the down-regulation of aortic endothelial antioxidants and NO generating system in rats.
本研究的目的是探讨慢性乙醇诱导的大鼠血压（BP）升高与主动脉一氧化氮（NO）及抗氧化系统改变之间的关系。将雄性Fisher大鼠（200 - 250克）分为两组，每组六只，处理如下：1）对照组（口服5%蔗糖），每日一次，共12周；2）20%乙醇组（口服4克/千克），每日一次，共12周。每周通过尾套法记录血压（收缩压、舒张压和平均压）。处理12周后处死动物，收集并分析胸主动脉。结果显示，与对照组相比，大鼠摄入乙醇12周后收缩压、舒张压和平均压显著升高。与对照组相比，乙醇处理组大鼠的内皮型一氧化氮合酶（eNOS）和血管内皮生长因子（VEGF）表达下调（为对照组的50 - 55%），导致主动脉NO水平降低（为对照组的69%）。与对照组相比，乙醇处理组大鼠主动脉中还原型谷胱甘肽与氧化型谷胱甘肽的比值（GSH/GSSG）显著降低（为对照组的58%）。主动脉GSH/GSSG比值的降低与血压升高显著相关（r = 0.69）。与对照组相比，乙醇处理组大鼠主动脉中的抗氧化酶：铜/锌超氧化物歧化酶（CuZn-SOD）、锰（Mn）-SOD、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）活性显著降低（为对照组的36 - 53%）。该研究得出结论，慢性乙醇摄入可诱发高血压，这与大鼠主动脉内皮抗氧化剂和NO生成系统下调导致的血管内皮功能障碍有关。
