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

背景：交感神经系统(SNS)是血管功能和健康的重要控制者。这种控制系统通过从神经释放被称为去甲肾上腺素(NE)和神经肽Y(NPY)的化学物质来发挥作用。NE和NPY的主要作用部位在称为小动脉或微血管的小动脉上。在去甲肾上腺素和神经肽Y收缩微血管的同时，内皮(血管内侧的细胞)竞相扩张(松弛)微血管。值得注意的是，到目前为止，还没有开发出在微血管水平上直接检查去甲肾上腺素和神经肽Y对活体动物的影响的实验模型。事实上，还没有人研究SNS和内皮系统在同一时间从饲喂血管到毛细血管床的共同作用。目的：我们将开发一种新的大鼠骨骼肌制剂，以实时表征去甲肾上腺素和神经肽Y对小动脉树所有水平的影响。此外，我们将研究内皮细胞如何单独和共同作用于去甲肾上腺素和神经肽Y。这项研究产生的数据将提供关于SNS和内皮对小动脉控制和小动脉和毛细血管中红细胞分布的影响的新的和有价值的信息。方法：在静息状态下，使用收缩和松弛血管的药物，用显微镜直接观察微血管。我们将从显微镜下拍摄各级血管和红细胞的视频，并使用专门设计的软件：1)表征NE和NPY对从供血动脉到毛细血管的微血管血流的影响；2)区分NE和NPY对红细胞分布的影响；3)描述内皮如何影响NE和NPY的功能作用。意义：从这个模型中产生的数据将提供关于内皮、NE和NPY在微血管系统中的完整和联合作用的第一手信息。除了获得对骨骼肌血流和血液动力学控制的新的和直接的见解外，这些实验数据将证实并建立我们目前在骨骼肌组织血流和氧气运输数学模型方面的努力。

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.