Regulation of peripheral vascular function

本研究计划的总体目标是了解外周血管系统及其所在组织的功能整合。 在身体的许多组织（例如，脑、心脏、骨骼肌）中，组织代谢和血流之间存在紧密耦合。 充足的血液流动是保持健康的工作环境以避免疲劳和损伤所必需的。 尽管人们对中枢血管控制了解很多，但令人惊讶的是，对维持适当细胞环境的微血管系统和周围组织之间的相互关系却知之甚少。 拟议的研究将使用骨骼肌及其相关的微血管系统来研究组织功能和外周血管功能之间的关系。 骨骼肌是研究这种关系的理想组织，因为它的代谢率可以很容易地在很大范围内改变。血流量和肌肉代谢是相关的，但这种关系的性质，这种关系如何随着肌肉活动的变化而变化，以及它如何随时间变化尚不清楚。 我们已经完成了一些研究，这些研究已经开始确定哪些收缩参数在确定增加血流量所需的血管舒张反应方面是最重要的。 我们现在建议实验继续定义收缩的重要扩张方面，并开始识别肌肉用于与血管系统通讯以引起这种血管扩张的血管扩张物质。 这项工作将有助于了解骨骼肌细胞和血管系统之间的沟通和协调，导致血流和运动之间的紧密耦合。 对骨骼肌的研究将有助于我们理解其他组织如何维持正常健康的工作环境。 了解正常条件下的组织功能是维持组织健康、防止组织损伤以及预防和治疗疾病的第一步。

The overall goal of this research program is to understand the integration of function of the peripheral vasculature and the tissue in which it resides.  A close coupling exists between tissue metabolism and blood flow in many tissues of the body (e.g. brain, heart, skeletal muscle).  Adequate blood flow is necessary to maintain the healthy working environment to avoid fatigue and damage.  Although much is known about central vascular control surprisingly little is known about the interrelationship between the microvasculature and the surrounding tissue which maintains a proper cellular environment.  The proposed studies will use skeletal muscle and its associated microvasculature to study the relationship between tissue function and peripheral vascular function.  Skeletal muscle is an ideal tissue in which to study this relationship because its metabolic rate can be easily changed through a large range. Blood flow and muscle metabolism are related but the nature of this relationship, how this relationship changes with changes in muscle activity and how it change over time are unclear.  We have completed studies which have started to define which parameters of contraction are most important in determining the vasodilatory response necessary to increase blood flow.  We now propose experiments continue to define the important dilatory aspects of contraction as well as begin to identify the vasodilator substances used by the muscle to communicate with the vasculature to cause this vasodilation.   This work will contribute to the understanding of the communication and coordination between skeletal muscle cells and the vasculature that results in the tight coupling between blood flow and exercise.  Work on skeletal muscle will help in our understanding of how other tissues maintain a normal healthy working environment.  Understanding tissue function under normal conditions is the first step in maintaining tissue health, preventing tissue damage and preventing and treating disease.