The increased prevalence of hypertension in obesity is not understood in detail. The regulation of vascular tone is essential to the regulation of tissue blood flow. The endothelium dependent (nitric oxide (NO)) vasorelaxation is impaired in a number of pathophysiolical conditions and may be involved also in human obesity. Previous studies suggest a relationship between impaired endothelium dependent vasorelaxation and abnormal FFA metabolism associated with insulin resistance to adipose tissue liplysis. Moreover, the vasculature may show an exaggerated response to vasoconstrictor stimuli either as a result of impaired vasodilatory counterregulation or independently. We hypothesize that endothtelium dependent vasorelaxation is impaired in normotensive, insulin resistant upper body obese subjects (known to be at increased risk of developing hypertension) as compared with age matched lean subjects. Furthermore, we hypothesize an increased sensitivity to vasoconstrictor stimulation in these obese subjects and that the degree of abnormal vasoregulation in associated with the degree insulin resistance to glucose and FFA metabolism. These proposals can be investigated using established techniques for measurement of forearm blood flow following brachial artery infusion of vasodilators and constrictors and using a two step hyperinsulinaemic euglycaemic clamp technique. The results from this investigation will provide a better understanding of the mechanisms governing the regulation of vascular tone in insulin resistant subjects with upper body obesity.
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