Effect of Diet on Oxidative Stress, NO and Hypertension

描述(由申请人提供)：本提案的具体目的是 研究高饱和脂肪饮食和饮食的潜在机制 精制碳水化合物(蔗糖)导致胰岛素抵抗和高血压 相比之下，饮食中含有大量未经精制的碳水化合物和低脂肪。高血压 折磨着美国四分之一的成年人口，是一种 心肌梗死、中风和充血性心脏的标志性危险因素 失败了。虽然其原因很大程度上还不清楚，但与胰岛素有关。 抵抗/高胰岛素血症、氧化应激和内皮功能障碍。这个 在这项拨款中要检验的主要假设是，一种高脂肪、精致的 碳水化合物饮食(HFS)增加了活性氧/氮的产生 导致胰岛素抵抗的物种(如ONOO-)以及 封闭和失活NO会导致高血压。为了测试这一点 假设，雄性和雌性大鼠将在HFS或低脂饲料中饲养， 复合碳水化合物饮食(LFCC)和血压将通过 尾部袖口和遥测方法。分离的动脉节段将用于 检测内皮功能。血浆/尿液测量将评估NO 代谢物、丙二醛和cGMP水平。生化研究将会是。在以下日期进行 包括主动脉、心脏和肾脏在内的多个组织测量eNOS、iNOS、nNOS 和超氧化物歧化酶蛋白、一氧化氮合酶和超氧化物歧化酶活性、硝基酪氨酸的形成和组织 CGMP水平。还将进行研究，以调查饮食的价值 修改(改用LFCC饮食或补充抗氧化剂)和 运动训练对控制高血压的作用以及热量的作用 限制高血压的发展。这些研究的结果 可能提供了一种机制来解释HFS类饮食是如何导致胰岛素抵抗的 和高血压，以及LFCC饮食、抗氧化治疗或运动训练 帮助控制胰岛素抵抗和高血压。

DESCRIPTION (provided by applicant): The specific aim of this proposal is to investigate potential mechanisms by which a diet high in saturated fat and refined carbohydrates (sucrose) induces insulin resistance and hypertension compared to a diet high in unrefined carbohydrate and low in fat. Hypertension afflicts one quarter of the adult population in the United States and is a hallmark risk factor for myocardial infarction, stroke and congestive heart failure. Although its cause is largely unknown, it is associated with insulin resistance/ hyperinsulinemia, oxidative stress and endothelial dysfunction. The primary hypothesis to be tested in this grant is that a high-fat, refined carbohydrate diet (HFS) increases the production of reactive oxygen/nitrogen species (e.g. ONOO-), contributing to insulin resistance, as well as sequestrating and inactivating NO leading to hypertension. To test this hypothesis, male and female rats will be raised on either the HFS or a low-fat, complex carbohydrate diet (LFCC) and blood pressure will be measured via the tail-cuff and telemetry methods. Isolated arterial segments will be used to test endothelial function. Plasma/urinary measurements will assess NO metabotites, MDA and cGMP levels. Biochemical studies will be. conducted on several tissues, including aorta, heart and kidney to measure eNOS, iNOS, nNOS and SOD proteins, NOS and SOD activities, nitrotyrosine formation and tissue cGMP levels. Studies will also be conducted to investigate the value of dietary modification (switching to an LFCC diet or antioxidant supplementation) and exercise training for controlling hypertension, as well as the role of caloric restriction on the development of hypertension. The results of these studies may provide a mechanism to explain how HFS type diets cause insulin resistance and hypertension, and how a LFCC diet, antioxidant therapy or exercise training aid in the control of insulin resistance and hypertension.