A novel integrative approach to the comprehensive study of skeletal muscle blood flow

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BACKGROUND: The sympathetic nervous system (SNS) is an important controller of vascular function and health. This control system exerts its effects by releasing chemicals from nerves called norepinephrine (NE) and neuropeptide Y (NPY). A major site of action for the NE and NPY is on small arteries called arterioles or microvessels. At the same time as NE and NPY constrict microvessels, the endothelium (cells on the inside of vessels) competes to dilate (relax) them. Remarkably, as of yet, few experimental models have been developed to directly examine the effects of NE and NPY in live animals at the microvascular level. In fact, no one has studied the SNS and endothelial systems acting together from feed vessel to capillary bed at one time. OBJECTIVES: We shall develop a new rat skeletal muscle preparation to characterize the impact of NE and NPY, on all levels of the arteriolar tree, in real-time. Furthermore, we will investigate how the endothelium interacts with NE and NPY, on their own and together. Data generated from this research will provide new and valuable information pertaining to the impact of the SNS and the endothelium on arteriolar control and red blood cell distribution in arterioles and capillaries. APPROACH: We shall directly observe the microvasculature using a microscope, under resting conditions, and with drugs that constrict and relax vessels. From the microscope we will take videos of the blood vessels and red blood cells at all levels, and using specially designed software we will: 1) characterize the impact of NE and NPY on microvascular blood flow, from feed arteries to capillaries; 2) differentiate the influence of NE and NPY on red blood cell distribution; and 3) describe how the endothelium can impact NE and NPYs functional role. SIGNIFICANCE: The data generated from this model will provide first hand information pertaining to the complete and combined role of the endothelium, NE, and NPY on the microvasculature. Besides gaining new and direct insight into the control of skeletal muscle blood flow and hemodynamics, this experimental data will confirm and build on our current departmental efforts in mathematical modeling of skeletal muscle tissue blood flow and oxygen transport.