VASCULAR METABOLISM AND ITS RELATION TO FUNCTION

描述：(改编自摘要)这项工作的总体目标 应用是研究特定的主要假设类别，这些假设可能 低氧对猪冠状动脉血管的扩张作用 (低氧性血管扩张)。特定的、假设的、氧气感应区 需要研究的是细胞内钙离子、pH的变化、 收缩装置的钙敏感性及其局限性 新陈代谢和高能磷酸根。拟议的研究将包括 低氧对细胞内钙和pH的影响 比例荧光染料技术与二者之间的关系 细胞内钙、肌球蛋白轻链磷酸化与等长 力及其对新陈代谢和磷胶原形态及含量的影响 利用分析性等速电泳法。进行的初步数据 日期表明，之前提出的主要机制中没有一项 包括钠泵和依赖于ATP的钾通道， 例如，这实际上是猪冠状动脉低氧血管松弛的基础 动脉。此外，初步证据还表明，随着刺激 由KCL引起的钙不变或实际上因低氧而增加 等轴力的减小。这些结果表明存在一种 猪冠状动脉通畅过程中的新型氧敏机制 肌肉。此外，应用程序中还提供了新的数据， 提示pH可能强烈影响血管对低氧的反应。在……里面 此外，这些工作人员已经确定了三种不同类型的 冠状动脉内皮细胞依赖的氧感应反应， 因此，他们提出的研究还包括对以下假设的测试 内皮细胞钙、pH或能量代谢的改变是其基础 这些不同的内皮细胞对氧气的依赖反应。这些信息是 不仅对血管生理学的基本了解很重要，而且 也为血管病理学开发了一种合理的治疗方法 包括血管痉挛疾病。

DESCRIPTION: (adapted from the abstract) The overall goal of this application is to study the specific major classes of hypotheses which may underlie the vasodilatory effect of hypoxia in porcine coronary arteries (hypoxic vasodilatation). The specific, hypothetical, oxygen sensing areas to be studied would be intracellular calcium, changes in pH, alteration of calcium sensitivity of the contractile apparatus and limitation of metabolism and high energy phosphagens. The proposed studies will include measurements of the effect of hypoxia on intracellular calcium and pH using ratiometric fluorescent dye techniques and the relationship between intracellular calcium, myosin light chain phosphorylation and isometric force and the effect on metabolism and phosphagen profiles and content utilizing analytical isotachophoresis. The preliminary data carried out to date suggest that none of the major mechanisms previously proposed including the sodium pump, and ATP-dependent potassium channels, for example, actually underlie the hypoxic vasorelaxation in porcine coronary artery. In addition, initial evidence also suggests that with stimulation by KCL calcium does not change or is actually increased by hypoxia despite a decrease in isometric force. These results suggest the existence of a novel type of oxygen sensing mechanism in porcine coronary artery smooth muscle. In addition there are new data presented in the application which suggest that pH may strongly influence vessel response to hypoxia. In addition, these workers have identified three distinct types of endothelium-dependent oxygen sensing responses in the coronary artery and, their proposed studies therefore also include tests of the hypotheses that alterations of endothelial cell calcium, pH, or energy metabolism underlie these various endothelium dependent response to oxygen. The information is important not only to the basic understanding of vascular physiology but also developing a rational therapeutic approach to vascular pathology including vasospastic disease.