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.
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