VASCULAR METABOLISM AND ITS RELATION TO FUNCTION

描述：（改编自摘要）这一总体目标 应用是研究特定的主要类别的假设， 缺氧对猪冠状动脉血管舒张作用的基础 （缺氧性血管舒张）。 特定的，假设的，氧气感应区域 要研究的是细胞内钙，pH值的变化， 收缩器的钙敏感性和限制 代谢和高能磷酸酶。 拟议的研究将包括 缺氧对细胞内钙和pH值的影响的测量， 比率荧光染料技术和 细胞内钙离子、肌球蛋白轻链磷酸化和等长收缩 力以及对代谢和磷酸化蛋白谱和含量的影响 利用分析等速电泳。进行的初步数据， 日期表明，以前提出的主要机制 包括钠泵和ATP依赖性钾通道， 例如，实际上是猪冠状动脉缺氧性血管舒张的基础 动脉 此外，初步证据还表明， 通过氯化钾钙不改变或实际上增加缺氧，尽管 等长收缩力下降。 这些结果表明存在一种 猪冠状动脉平滑肌一种新的氧敏感机制 肌肉. 此外，申请中还提供了新的数据， 提示pH值可能强烈影响血管对缺氧反应。 在 此外，这些工作人员还确定了三种不同类型的 冠状动脉中的内皮依赖性氧传感反应， 因此，他们提出的研究还包括对假设的检验， 内皮细胞钙、pH或能量代谢的改变是 这些不同的内皮细胞对氧气的依赖性反应。 信息 不仅对血管生理学的基本理解很重要， 也为血管病理学发展了合理的治疗方法， 包括血管痉挛性疾病。

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.