Oxidative stress in a rat model of obesity-induced hypertension
Oxidative stress in a rat model of obesity-induced hypertension
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DOI：
10.1161/01.hyp.37.2.554
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发表时间：
2001-02-01
期刊：
影响因子：
8.3
通讯作者：
Prewitt, RL
中科院分区：
文献类型：
--
作者：
Dobrian, AD;Davies, MJ;Prewitt, RL
肥胖引起高血压的机制尚不完全清楚。我们最近报道了饮食诱发肥胖的大鼠模型中高血压的发生。当Sprague-Dawley大鼠（n=60）喂食中等高脂肪饮食（32 kcal%脂肪）10至16周时，大约一半的大鼠出现肥胖（肥胖倾向[OP]组）和轻度高血压（158+/-3.4 mmHg收缩压），而另一半（肥胖抵抗[OR]组）维持与低脂对照组相当的体重且血压正常（135.8+/-3.8 毫米汞柱）。我们在该模型中研究了氧化应激在高血压发展中的潜在作用。作为硫代巴比妥酸反应物质测量的脂质过氧化物显示，与 OR 和对照大鼠（0.9+/-0.3 nmol 丙二醛/mg 蛋白质）相比，OP 大鼠的 LDL 分数（2.8+/-0.32 nmol 丙二醛/mg 蛋白质）显着增加。此外，经过 16 周的饮食后，OP 大鼠的主动脉和肾脏硫代巴比妥酸反应物质显着增加（3 倍和 5 倍）。此外，通过光泽精发光测量的主动脉环产生的超氧化物显示，与 OR 组和对照组相比，OP 组增加了 2 倍。此外。肾脏中游离异前列烷排泄和硝基酪氨酸仅在 OP 大鼠中显示增加。通过LDH法测量的尿液和血浆硝酸盐/亚硝酸盐显示OP大鼠比OR大鼠降低1.8倍。然而，通过逆转录酶-聚合酶链反应评估的肾皮质和髓质内皮NO合酶表达显示，与OR和对照大鼠相比，OP大鼠的肾皮质和髓质内皮NO合酶表达显着增加（OP大鼠的内皮NO合酶/β-肌动蛋白比率为1.3+/-0.04，而OR大鼠为0.44+/-0.02），这表明该酶可能转向产生超氧化物。总的来说，数据显示 OP 动物的 NO 生物利用度降低，部分原因是氧化应激增加。
The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity. When Sprague-Dawley rats (n=60) are fed a moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approximately half of them develop obesity (obesity-prone [OP] group) and mild hypertension (158+/-3.4 mmHg systolic pressure), whereas the other half (obesity-resistant [OR] group) maintains a body weight equivalent to that of a low fat control group and is normotensive (135.8+/-3.8 mm Hg). We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid-reactive substances showed a significant increase in the LDL fraction of OP rats (2.8+/-0.32 nmol malondialdehyde/mg protein) compared with OR and control rats (0.9+/-0.3 nmol malondialdehyde/mg protein). Also, aortic and kidney thiobarbituric acid-reactive substances showed a significant (3- and 5-fold) increase in OP rats after 16 weeks of diet. In addition, superoxide generation by aortic rings, measured by lucigenin luminescence, showed a 2-fold increase in the OP group compared with both the OR and control groups. In addition. free isoprostane excretion and nitrotyrosine in the kidney showed an increase in OP rats only. The urine and plasma nitrate/nitrite measured by the LDH method showed a 1.8-fold decrease in OP rats compared with OR rats. However, endothelial NO synthase expression in the kidney cortex and medulla assessed by reverse transcriptase-polymerase chain reaction showed a strong increase in the OP rats versus OR and control rats (endothelial NO synthase/beta -actin ratio 1.3+/-0.04 in OP rats versus 0.44+/-0.02 in OR rats), suggesting a possible shift toward superoxide production by the enzyme. Collectively, the data show a decreased NO bioavailability in OP animals that is due in part to the increased oxidative stress.