Roberts Christian K, Vaziri Nosratola D, Sindhu Ram K, Barnard R James
Department of Physiological Science, University of California, Los Angeles 90095, USA.
J Appl Physiol (1985). 2003 Mar;94(3):941-6. doi: 10.1152/japplphysiol.00536.2002. Epub 2002 Oct 25.
Chronic consumption of a high-fat, refined-carbohydrate (HFS) diet causes hypertension. In an earlier study, we found increased nitric oxide (NO) inactivation by reactive oxygen species (ROS) and functional NO deficiency in this model. Given the critical role of NO in renal sodium handling, we hypothesized that diet-induced hypertension may be associated with salt sensitivity. Female Fischer rats were fed an HFS or a standard low-fat, complex-carbohydrate (LFCC) rat chow diet starting at 2 mo of age for 2 yr. Arterial blood pressure, renal neuronal NO synthase (nNOS), endothelial NO synthase (eNOS), and inducible NO synthase (iNOS) protein and nitrotyrosine abundance (a marker of NO inactivation by ROS), and urinary NO metabolite excretion were measured. To assess salt sensitivity, the blood pressure response to a high-salt (4%) diet for 1 wk was determined. After 2 yr, renal nNOS and urinary NO metabolite excretion were significantly depressed, whereas arterial pressure, eNOS, iNOS, and nitrotyrosine were elevated in the HFS group but remained virtually unchanged in the LFCC group. Consumption of the high-salt diet resulted in a significant rise in arterial pressure in the HFS, but not in the LFCC, group. Thus chronic consumption of an HFS diet results in hypertension and salt sensitivity, which may be in part due to a combination of ROS-mediated NO inactivation and depressed renal nNOS protein expression.
长期食用高脂肪、精制碳水化合物（HFS）饮食会导致高血压。在早期的一项研究中，我们发现该模型中活性氧（ROS）使一氧化氮（NO）失活增加以及功能性NO缺乏。鉴于NO在肾脏钠处理中的关键作用，我们推测饮食诱导的高血压可能与盐敏感性有关。雌性Fischer大鼠从2月龄开始喂食HFS或标准低脂、复合碳水化合物（LFCC）大鼠饲料，持续2年。测量动脉血压、肾神经元型一氧化氮合酶（nNOS）、内皮型一氧化氮合酶（eNOS）和诱导型一氧化氮合酶（iNOS）蛋白以及硝基酪氨酸丰度（ROS使NO失活的标志物），并检测尿中NO代谢产物排泄。为了评估盐敏感性，测定了对高盐（4%）饮食1周的血压反应。2年后，HFS组肾nNOS和尿中NO代谢产物排泄显著降低，而动脉压、eNOS、iNOS和硝基酪氨酸升高，而LFCC组几乎没有变化。食用高盐饮食导致HFS组动脉压显著升高，但LFCC组未升高。因此，长期食用HFS饮食会导致高血压和盐敏感性，这可能部分归因于ROS介导的NO失活和肾nNOS蛋白表达降低的共同作用。
