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）产生和释放许多控制动脉功能的物质。 特别是，内皮细胞产生内皮源性舒张因子（EDRF）和收缩因子（EDCF），控制动脉如何舒张和收缩以调节血流。 有必要发现这些因素是如何产生的，以及它们如何控制血管功能。一种可能的“主调节器”可能是一种名为AMP激活蛋白激酶（AMPK）的分子。 关于AMPK如何影响动脉功能知之甚少，但拟议的研究将发现AMPK影响EDRF和EDCF活性和血管功能的方式。我们的实验方法使用完整的大鼠和从大鼠分离的动脉。 将使用具有正常和功能障碍内皮的不同类型的血管来更好地了解控制AMPK和EDRF/EDCF平衡的因素。 这项工作的另一个独特之处是，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有明确的有益影响，但使其成为可能的动脉细胞的变化尚不清楚。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响应许多压力而变化非常重要。 因此，生物学家和血管生理学家将对这项研究产生最直接的兴趣。 预计，由于正在研究的许多信号在各种其他组织和条件下也很重要，因此许多结果将对世界各地的科学家产生广泛的兴趣和重要性。 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，使加拿大人感兴趣和重要的研究。

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.