EFFECT OF PHYSICAL INACTIVITY ON ENDOTHELIAL FUNCTION

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。 理论基础：久坐不动的生活方式是冠状动脉疾病和糖尿病发展的一个重要且日益严重的危险因素。缺乏运动会导致糖尿病和冠状动脉疾病，这一事实表明存在共同的病理生理机制。从久坐不动的生活方式导致动脉粥样硬化增加的途径还不完全清楚。内皮功能障碍是动脉粥样硬化发展过程中的关键步骤，也是急性冠状动脉事件的发病机制之一。卧床休息是一种既定的研究方法，用于模拟不活动的生理效应。先前的研究表明，卧床休息会导致胰岛素抵抗，这是一种已知与内皮功能障碍有关的糖尿病前期状态。到目前为止，还没有研究对运动不足对血管功能和胰岛素信号的影响进行详细的调查。因此，我们现在建议研究卧床休息对健康受试者内皮功能的影响。 假设：我们假设短时间的不活动将损害内皮功能，其证据是内皮依赖性的臂动脉血流介导的扩张减少。我们假设，血管扩张特性的改变将与胰岛素抵抗标志物的增加、细胞燃料感受性的降低和炎症标志物的增加有关。 实验设计：这项研究将考察5天卧床休息对健康个体血管系统的影响。我们建议招募15名健康人，他们将在卧床前和卧床5天后进行血管功能超声检查和胰岛素检测，并进行葡萄糖耐量试验。

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. Rationale: Sedentary lifestyle is an important and growing risk factor for the development of coronary artery disease and diabetes. The fact that physical inactivity contributes to both diabetes and coronary artery disease suggests the presence of common pathophysiologic mechanisms. The pathways leading from a sedentary lifestyle to increased atherogenesis are incompletely understood. Endothelial dysfunction is a critical step in the development of atherosclerosis and contributes to the pathogenesis of acute coronary events. Bedrest is an established research method used to simulate the physiologic effects of inactivity. Previous studies show that bedrest induces insulin resistance, a prediabetic state known to be associated with endothelial dysfunction. To date no study has conducted a detailed investigation of the impact of physical inactivity on vascular function and insulin signaling. Thus, we now propose to study the effect of bedrest on endothelial function in healthy subjects. Hypotheses: We hypothesize that a short period of inactivity will impair endothelial function as evidenced by a decrease in endothelium-dependent brachial artery flow-mediated dilation. We hypothesize that the changes in vasodilatory properties will be seen in association with an increase in markers of insulin resistance, decrease in cellular fuel sensing, and an increase in inflammatory markers. Experimental Design: The study will examine the effects of a 5 day period of bedrest on the vasculature in healthy individuals. We propose to enroll 15 healthy individuals who will have tests of blood vessel function using ultrasonography and insulin sensing using a glucose tolerance tests before and after 5 days of bedrest.