The role of shear stress and sympathetic nervous activity in the regulation of human arterial function and structure

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Our arteries are lined by a single layer of cells called the vascular endothelium. Due to their position on the inside of the artery, the endothelial cells are constantly exposed to the frictional force created by the flowing blood. Termed shear stress, this frictional force plays a key role in regulating endothelial cell responses that change artery size and stiffness in both the short and the long term. We are interested in understanding the sensitivity of the endothelium to changes in shear stress, the speed of its responses and how these factors may differ in arteries that are in the arms vs. the legs. We will use cutting edge Doppler ultrasound technology to measure both changes in shear stress and changes in artery size and stiffness. In daily living, the most common cause of increases in shear stress is performing exercise. Exercise also results in long term changes in artery function and structure, however, we do not know if these changes are brought about by increases in shear stress per se, or other variables that change with exercise. We will isolate the role of shear stress in changes in artery function with a novel technique that allows us to mimic exercise induced changes in shear stress without having to perform contractions. In addition to responding to changes in shear stress, our arteries are also controlled by nerves. Similar to the motor neurons that that stimulate our skeletal muscles to contract, the nerves that control our arteries cause the muscle in their walls to contract, making the vessel smaller. We still do not clearly understand the ways in which responses to increases in shear stress, and responses to signals from the nerves interact when they are experienced simultaneously in the same artery. In experiments we will manipulate both variables, and measure changes in artery size and factors in the blood that reflect neural and endothelial cell function. This will give us important insight into the complex interaction and integration of signals in our arteries. The information gained from these studies will assist in advancing our understanding of basic human cardiovascular function.