EFFECT OF PHYSICAL INACTIVITY ON ENDOTHELIAL FUNCTION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。基本原理：久坐的生活方式是冠状动脉疾病和糖尿病发展的一个重要且不断增长的风险因素。缺乏身体活动导致糖尿病和冠状动脉疾病的事实表明存在共同的病理生理机制。从久坐的生活方式导致动脉粥样硬化形成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的关键步骤，并有助于急性冠状动脉事件的发病机制。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，卧床可诱导胰岛素抵抗，这是一种已知与内皮功能障碍相关的糖尿病前期状态。到目前为止，还没有研究详细调查身体活动对血管功能和胰岛素信号的影响。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，短时间的不活动会损害内皮功能，这可以通过内皮依赖性肱动脉血流介导的舒张功能的降低来证明。我们假设血管舒张特性的变化与胰岛素抵抗标志物的增加、细胞燃料传感的减少和炎症标志物的增加相关。 实验设计：本研究将检查5天卧床休息对健康个体血管系统的影响。我们计划招募15名健康受试者，他们将在卧床休息5天之前和之后使用超声检查和使用葡萄糖耐量试验的胰岛素传感进行血管功能测试。

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.