Control Mechanisms of Vascular Endothelial Function

控制血管是调节心血管系统的关键。构成血管的细胞（内皮细胞和血管平滑肌细胞）产生并释放许多控制动脉功能的物质。特别是，内皮细胞产生内皮来源的放松因子（edrf）和收缩因子（edcf），它们控制动脉如何放松和收缩以调节血液流动。有必要发现这些因子是如何产生的以及它们是如何控制血管功能的。一种可能的“主调节器”可能是一种被称为amp活化蛋白激酶（AMPK）的分子。关于AMPK如何影响动脉功能，我们知之甚少，但我们提出的研究将发现AMPK如何影响EDRF和EDCF活性以及血管功能。我们的实验方法使用完整的大鼠和从大鼠身上分离出来的动脉。不同类型的血管正常和不正常的内皮将被用来更好地了解控制AMPK和EDRF/EDCF平衡的因素。这项工作的另一个独特之处在于，我们还将研究控制EDRF和EDCF活动的因素对运动训练的适应性。这一点很重要，因为尽管运动对动脉功能的有益影响已经得到证实，但导致这种可能的动脉细胞变化尚不清楚。这项研究对于了解控制动脉功能的基本机制，以及为什么动脉功能会随着一些压力而改变是很重要的。因此，这项研究将是生物学家和血管生理学家最感兴趣的。由于许多正在研究的信号在各种其他组织和条件中也很重要，因此可以预期，许多结果将引起全世界科学家的广泛兴趣和重要性。这种基本的科学理解，以及临床研究人员将其转化为应用的潜力，使加拿大人对这项研究感兴趣和重要。

Control of blood vessels is key to regulating the cardiovascular system. The cells that make up the blood vessels (endothelial cells and vascular smooth muscle cells) produce and release a number of substances that control the function of the arteries. In particular, the endothelial cells produce both Endothelium-Derived Relaxing Factors (EDRFs) and Contracting Factors (EDCFs) that control how arteries relax and contract to regulate blood flow. It is necessary to discover how these factors are produced and how they control blood vessel function. One possible 'master regulator' could be a molecule called AMP-activated protein kinase (AMPK). Very little is known regarding how AMPK affects artery function, but the proposed research will discover ways in which AMPK affects EDRF and EDCF activity and vascular function. Our experimental approach uses intact rats and arteries isolated from rats. Different types of blood vessels with normal and dysfunctional endothelium will be used to better understand the factors controlling AMPK, and EDRF/EDCF balance. Another unique feature of this work is that we will also study adaptations in the factors controlling EDRF and EDCF activity to exercise training. This is important because although there is a well-established beneficial effect of exercise on artery function, the changes in the artery cells that make this possible are not known. This research is important in order to understand the basic mechanisms controlling artery function, and why artery function changes in response to a number of stresses. Thus, the research will be most immediately of interest to biologists and vascular physiologists. It is anticipated that, because many of the signals being studied are of importance in a variety of other tissues and conditions as well, that many of the results will be of widespread interest and importance to scientists around the world. This basic science understanding, and potential for it to be translated into applications by clinical researchers make the research of interest and importance to Canadians.