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 精制碳水化合物（蔗糖）诱导胰岛素抵抗和高血压 与高碳水化合物低脂肪的饮食相比。高血压 美国四分之一的成年人患有这种疾病， 心肌梗死、中风和充血性心脏的标志性危险因素 失败虽然其原因在很大程度上是未知的，但它与胰岛素有关 抵抗/高胰岛素血症、氧化应激和内皮功能障碍。的 在这项资助中要检验的主要假设是，一种高脂肪、精制的 碳水化合物饮食（HFS）增加活性氧/氮的产生 种（例如ONOO-），导致胰岛素抵抗，以及 螯合和灭活NO导致高血压。为了验证这一 假设，雄性和雌性大鼠将在HFS或低脂， 复合碳水化合物饮食（LFCC）和血压将通过 尾套和遥测方法。隔离动脉段将用于 检测内皮功能。血浆/尿液测量将评估NO 代谢物、MDA和cGMP水平。生物化学研究将是。上进行 几种组织，包括主动脉、心脏和肾脏，以测量eNOS、iNOS、nNOS NOS和SOD活性，硝基酪氨酸形成和组织 cGMP水平。还将进行研究，以调查膳食营养素的价值。 修改（改用低脂肪酸钙饮食或补充抗氧化剂）， 运动训练对控制高血压的作用，以及热量 限制高血压的发展。这些研究的结果 可以提供一种机制来解释HFS型饮食如何导致胰岛素抵抗 和高血压，以及LFCC饮食，抗氧化治疗或运动训练 有助于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.