Metabolic Regulation of Muscle Blood Flow

外周循环的血液流动受到调节，以维持营养物质输送和组织代谢需求之间的平衡。血液流向新陈代谢活跃的组织。这种增加的血流量是末端小动脉直径增加和上游血管变大的结果。末端小动脉似乎决定了血流的分布，而上游或“补给”血管在调节总组织血流方面更重要。随着新陈代谢的增加，血管活性代谢物从组织中释放出来。虽然已知血管活性代谢物会影响末端小动脉的直径，但代谢因子调节上游小动脉直径的机制尚不确定。我们实验室和其他人最近的研究表明，血管活性物质在小静脉-小动脉扩散中起重要作用。本提案中概述的研究将检验以下工作假设。在血流和组织代谢不匹配的情况下，静脉内皮细胞直接或间接地感知到PO2的降低和/或PCO2和H+的升高，从而释放出血管活性代谢物花生四烯酸，调节邻近小动脉的张力。拟议的研究将利用最近开发的原位微循环技术来验证这一假设，其中我们能够选择性地去除静脉内皮并评估对血流调节的影响。提出的研究将验证两个特定的假设：1)小静脉内皮释放一种花生四烯酸代谢物，这种代谢物从小静脉扩散到小动脉，引起小动脉扩张，以响应组织代谢率的增加。2)静脉内皮直接或间接地对缺氧、高碳酸血症和酸中毒作出反应，启动静脉内皮细胞释放一种或多种血管活性因子。这些研究应该提供新的和重要的信息，与我们理解内皮衍生因子在血流调节中的小静脉-小动脉扩散的重要性有关。

The blood flow to the peripheral circulation is regulated to maintain a balance between the delivery of nutrients and the metabolic demands of the tissue. Blood flow increases to a metabolically active tissue. This increased blood flow is the result of an increase in arteriolar diameter of terminal arterioles and larger upstream vessels. The terminal arterioles appear to determine distribution of flow while the upstream or "feed" vessels are more important in regulating total tissue flow. With an increase in metabolism there is the release of vasoactive metabolites from the tissue. Although vasoactive metabolites are known to affect the diameters of terminal arterioles the mechanisms by which metabolic factors regulate the diameter of upstream arterioles is uncertain. Recent studies from our lab and others have indicated an important role for the venular-arteriolar diffusion of vasoactive substances. The studies outlined in this proposal will test the following working hypothesis. In response to mismatches in blood flow and tissue metabolism, decreases in PO2 and/or increases in PCO2 and H+ are directly or indirectly sensed by the venular endothelial cells, resulting in the release of vasoactive metabolites of arachidonic acid which regulate the tone of adjacent arterioles. The proposed studies will test this hypothesis utilizing recently developed in situ microcirculatory techniques in which we are able to selectively remove the venular endothelium and assess the impact on blood flow regulation. The proposed studies will test two specific hypotheses: 1) The venular endothelium releases a metabolite of arachidonic acid that diffuses from the venule to the arteriole to cause an arteriolar dilation in response to an increase in tissue metabolic rate. 2) The venular endothelium responds to hypoxia, hypercapnia, and acidosis, directly, or indirectly to initiate the release of one or more vasoactive factors from the venular endothelial cells. These studies should provide new and important information relevant to our understanding the importance of venular-arteriolar diffusion of endothelial derived factors in the regulation of blood flow.