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

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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.