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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 本项目的具体目的是：1）确定增加FFA（剂量反应）对血压正常的肥胖受试者的血压、内皮功能和交感神经系统活动的影响。 在肥胖血压正常受试者中，以10、20和40 ml/h的速率增加Intralidid 20%溶液输注速率与生理盐水（40 ml/h）输注速率8小时期间，将测定BP、内皮功能和自主活动的变化。 将通过测量肱动脉血流介导的扩张直接评估内皮功能，并通过血管炎症标志物和氧化应激的变化间接评估内皮功能。 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）确定乳糜微粒衍生的FFA间歇性流入对肥胖血压正常受试者的血压、内皮功能和交感神经系统活动的影响。 在餐后脂血症期间，由肠乳糜微粒转运的膳食甘油三酯被内衬血管床的脂蛋白脂肪酶水解，随后释放FFA以转运穿过内皮。 将检查FFA的这种间歇性流量是否具有与Intraperoid输注相同的影响。 先验地，鉴于富含磷脂酰肌醇的脂蛋白与内皮的直接相互作用，我们预期对于相同的FFA通量，效果将更显著。 在8小时内每2小时重复口服脂肪负荷期间，将测定BP、内皮功能和自主活动的变化。 目的是使FFA浓度较基线增加2- 3倍（约1.5 mmol/L）。 将通过测量肱动脉血流介导的扩张直接评估内皮功能，并通过血管炎症标志物和氧化应激的变化间接评估内皮功能。 将通过心率变异性的功率谱分析评价心脏自主神经系统。

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.