PRESSOR EFFECTS OF FATTY ACIDS

该项目将检验肝细胞游离脂肪酸的假设 血压水平是血压的一个重要决定因素。假说 预测内脏或腹部肥胖与 高血压是因为内脏脂肪细胞将它们的脂肪酸释放到 门静脉循环，导致肝脏脂肪酸显著增加 内容。相比之下，体重较低的肥胖者，其风险 对于高血压来说，应该有较低的肝脏脂肪酸水平。 我们实验室的初步数据表明，长期输注 链状游离脂肪酸导致大鼠血压升高和 肝脏游离脂肪酸水平升高。这个项目的特点是 高脂肪酸血症与高血压的关系及检测 肝脏脂肪酸含量是否是血液的重要决定因素 压力。 有意识的、有仪器化的老鼠将被研究。脂肪酸输注 解决方案或载体进入全身和门静脉循环将是 根据它们对血压的影响进行评估。系统性的 对脂肪酸高血压的局部血流动力学反应将是 一旦确定，相关的肾脏和激素变化将 量过了。建立剂量反应曲线之间的关系 将确定注入的脂肪酸的量和升压反应 包括全身和门静脉输液。在单独的实验中，等离子体和 与高血压反应相关的组织脂肪酸水平 将会被确定。不同长链和中链脂肪的输注 将进行酸化以评估饱和或链长 注入的脂肪酸会影响升压反应。长期 然后进行脂肪酸的输注，以确定 慢性高血压是可以诱发的。 为了确定脂肪酸和胰岛素之间的关系 抵抗，使用最小胰岛素模型的体内研究 将采取敏感措施。脂肪酸时的胰岛素敏感性 输液将与车辆输液时的敏感性进行比较。在……里面 将进行体外研究，以评估脂肪酸对 血管反应性。此外，活体处理的动物血管 将用脂肪酸输注的血管与对照组的血管进行比较 动物。瘦肉和肥胖动物禁食对肝脏的影响 将测定脂肪酸含量和血压。脂肪酸 输液和依托莫昔尔将用于维持肝脏脂肪酸水平 在禁食三天期间喂食动物的范围内。这些研究 将决定维持肝脏脂肪酸水平是否能防止 血压的降低和胰岛素敏感性的增加 通常在禁食时发生。将使用尼古丁酸来减少 肥胖、高血压大鼠肝脏游离脂肪酸含量及其对血液的影响 压力和肝脏FFA含量将被测定。 这些研究应该描述脂肪酸的升压作用和 深入了解脂肪酸在高血压中的作用 腹部肥胖症。

This project will test the hypothesis that hepatocellular free fatty acid levels are an important determinant of blood pressure. The hypothesis predicts that visceral or abdominal obesity is strongly associated with hypertension because visceral fat cells release their fatty acids into the portal circulation, causing a marked increase in hepatic fatty acid content. By contrast, individuals with lower body obesity, whose risk for hypertension is low, should have lower hepatic fatty acid levels. Preliminary data from our laboratory demonstrate that infusion of long chain free fatty acids into rats results in elevated blood pressure and increased hepatic free fatty acid levels. This project will characterize the hypertension associated with fatty acid infusion and determine whether hepatic fatty acid content is a significant determinant of blood pressure. Conscious, instrumented rats will be studies. Infusions of fatty acid solution or vehicle into the systemic and portal circulations will be assessed with regard to their effects on blood pressure. The systemic and regional hemodynamic responses to fatty acid hypertension will be determined and the associated renal and hormonal changes will be measured. Dose response curves to establish the relationship between amount of fatty acid infused and pressor response will be determined for both systemic and portal infusions. In separate experiments, plasma and tissue levels of fatty acids associated with the hypertensive response will be determined. Infusions of different long and medium chain fatty acids will be performed to assess whether saturation or chain length of the infused fatty acid influences the pressor response. Long term infusions of fatty acids will then be performed to ascertain whether chronic hypertension can be induced. In order to determine the relationship between fatty acids and insulin resistance, in vivo studies using the minimal model of insulin sensitivity will be undertaken. Insulin sensitivity during fatty acid infusion will be compared with sensitivity during vehicle infusion. In vitro studies will be performed to assess the effects of fatty acids on vascular reactivity. In addition, vessels from animals treated in vivo with fatty acid infusion will be compared to vessels from control animals. The effect of fasting in lean and obese animals on hepatic fatty acid content and blood pressure will be determined. Fatty acid infusions and etomoxir will be used to maintain hepatic fatty acid levels in the range seen in fed animals during a three day fast. These studies will determine whether maintaining hepatic fatty acid levels prevents the decrease in blood pressure and the increase in insulin sensitivity which normally occurs with fasting. Nicotinin acid will be used to decrease hepatic FFA content in obese, hypertensive rats, and its effects on blood pressure and hepatic FFA content will be determined. These studies should characterize the pressor effects fatty acids and provide insight into the role of fatty acids in the hypertension of abdominal obesity.