FREE FATTY ACIDS-INDUCED HYPERTENSION AND ENDOTHELIAL DYSFUNCTION IN OBESE SUBJT

肥胖受试者中游离脂肪酸诱发的高血压和内皮功能障碍

• 批准号: 7603683
• 负责人: Guillermo E Umpierrez
• 金额: $ 0.46万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603683
• 关键词: Autonomic nervous system; Blood Vessels; Cardiac; Chylomicrons; Computer Retrieval of Information on Scientific Projects Database; Dilatation - action; Dose; Endothelium; Fat emulsion; Fatty acid glycerol esters; Functional disorder; Funding; Grant; Heart Rate; Hour; Hydrolysis; Hypertension; Inflammatory; Infusion procedures; Institution; Intestines; Lipoproteins; Measures; Mediating; Nonesterified Fatty Acids; Normal saline; Obesity; Oral; Oxidative Stress; Pathological Dilatation; Rate; Research; Research Personnel; Resources; Solutions; Source; Sympathetic Nervous System; Triglycerides; United States National Institutes of Health; brachial artery; lipoprotein lipase; normotensive; response; vascular bed

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims of this project are 1) to determine the effects of increasing FFA (dose response) on BP, endothelial function and sympathetic nervous system activity in obese normotensive subjects. Changes in BP, endothelial function, and autonomic activity will be determined during increasing infusion rates of Intralipid 20% solution at 10, 20, and 40 ml per hour vs. normal saline (40 ml/hr) for 8 hours in obese normotensive subjects. Endothelial function will be assessed directly by measuring brachial artery flow-mediated dilatation, and indirectly by changes on vascular inflammatory markers and oxidative stress. The cardiac autonomic nervous system will be evaluated by power spectral analysis of heart rate variability and 2) to determine the effects of intermittent influx of chylomicron-derived FFA on BP, endothelial function and sympathetic nervous system activity in obese normotensive subjects. During postprandial lipemia, dietary triglycerides transported by intestinal chylomicrons are hydrolyzed by lipoprotein lipase lining the vascular bed with subsequent release of FFA for transport across the endothelium. Whether this intermittent flux of FFA can have the same impact as the Intralipid infusion will be examined. A priori we expect that the effect would be more pronounced for the same FFA flux in view of the direct interactions of triglyceride-rich lipoproteins with the endothelium. Changes in BP, endothelial function, and autonomic activity will be determined during repeated oral fat loads every 2 hours for 8-hours. The aim would be to increase FFA concentrations by 2- to 3-fold (approx 1.5 mmol/L) from baseline. Endothelial function will be assessed directly by measuring brachial artery flow-mediated dilatation, and indirectly by changes on vascular inflammatory markers and oxidative stress. The cardiac autonomic nervous system will be evaluated by power spectral analysis of heart rate variability.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的具体目的是1）确定FFA（剂量反应）增加对肥胖受试者BP，内皮功能和交感神经系统活动的影响。 BP，内皮功能和自主活动的变化将在每小时10、20和40 mL溶液的输注率增加期间，而在肥胖的受试者中，每小时10、20和40 mL的溶液（40 mL/hr）在8小时内确定。 内皮功能将通过测量臂动脉流介导的扩张直接评估，并通过血管炎症标记和氧化应激的变化间接评估。 心率变异性的功率谱分析将评估心脏自主神经系统，2）确定乳糜微粒衍生的FFA间歇性涌入对BP的影响，内皮功能和交感神经系统对肥胖的正常受试者的影响。 在餐后脂肪血症期间，由肠梗传输的饮食甘油三酸酯通过脂蛋白脂肪酶水解血管床，随后释放出FFA，用于横跨内皮细胞。 FFA的间歇性通量是否可以与脂质内输注相同的影响。 先验的是，鉴于富含甘油三酸酯的脂蛋白与内皮的直接相互作用，对于相同的FFA通量，这种效果会更明显。 BP，内皮功能和自主活动的变化将在每2小时重复口腔脂肪载荷期间确定8小时。 目的是将FFA浓度从基线增加2至3倍（约1.5 mmol/L）。 内皮功能将通过测量臂动脉流介导的扩张直接评估，并通过血管炎症标记和氧化应激的变化间接评估。 心率变异性的功率谱分析将评估心脏自主神经系统。