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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本项目的具体目的是：1)确定增加FFA(剂量反应)对正常血压肥胖受试者的血压、内皮功能和交感神经系统活动的影响。在肥胖的正常血压受试者中，血压、内皮功能和自主神经活动的变化将在以每小时10、20和40毫升的Intralipid溶液与生理盐水(40毫升/小时)的输注速度增加8小时的过程中被测定。内皮功能将直接通过测量肱动脉血流介导的扩张来评估，并间接通过血管炎症标记物和氧化应激的变化来评估。将通过心率变异性的功率谱分析来评估心脏自主神经系统，以及2)确定间歇性注入乳糜管衍生的FFA对正常血压肥胖受试者的血压、内皮功能和交感神经系统活动的影响。在餐后血脂期间，肠道乳糜粒运输的饮食甘油三酯被血管床内的脂蛋白脂肪酶降解，随后释放游离脂肪酸，通过内皮运输。这种间歇性的FFA流量是否能产生与Intralipid输注相同的影响将被研究。鉴于富含甘油三酯的脂蛋白与血管内皮细胞的直接相互作用，我们预计对于相同的FFA流量，这种影响会更明显。在持续8小时的重复口服脂肪负荷过程中，将测定血压、内皮功能和自主神经活动的变化。其目标是将游离脂肪酸浓度从基线水平提高2至3倍(约为1.5mmoL/L)。内皮功能将直接通过测量肱动脉血流介导的扩张来评估，并间接通过血管炎症标记物和氧化应激的变化来评估。心脏自主神经系统将通过心率变异性的功率谱分析进行评估。

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.