RESPONSIVITY OF FOREARM RESISTANCE VESSELS IN UPPER BODY OBESITY

肥胖患者高血压患病率增加的原因尚不清楚。血管张力的调节对组织血流量的调节至关重要。内皮依赖的（一氧化氮（NO））血管松弛在许多病理生理条件下受损，也可能与人类肥胖有关。先前的研究表明，内皮依赖性血管松弛受损与脂肪组织脂解的胰岛素抵抗相关的FFA代谢异常之间存在关系。此外，血管系统可能对血管收缩刺激表现出过度反应，这可能是血管舒张反调节受损的结果，也可能是独立的结果。我们假设，与年龄匹配的瘦受试者相比，正常血压、胰岛素抵抗的上半身肥胖受试者（已知患高血压的风险增加）的内皮依赖性血管松弛受损。此外，我们假设这些肥胖受试者对血管收缩剂刺激的敏感性增加，并且血管调节异常的程度与葡萄糖和FFA代谢的胰岛素抵抗程度有关。这些建议可以使用已建立的技术来测量肱动脉输注血管扩张剂和收缩剂后的前臂血流量，并使用两步高胰岛素血症血糖钳技术。本研究的结果将有助于更好地理解胰岛素抵抗上半身肥胖患者血管张力调节的机制。

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.