INTERCELLULAR COORDINATION OF BLOOD FLOW CONTROL

描述：（改编自研究者摘要）： 这个项目是为了确定细胞和分子机制，支配 血流控制的整合和协调。电气和血管 反应沿小动脉和供血动脉迅速沿着传导， 协调阻力网络中的血管舒张和血管收缩。的 工作假设是传导反映了 通过间隙超极化（扩张）或去极化（收缩 内皮细胞（EC）和平滑肌细胞（SMC）之间的连接 组成血管壁的细胞EC和SMC层在传导中的作用是 不清楚，正如各个层之间的耦合的性质一样。此外，本发明还 仓鼠颊囊上皮微血管之间的传导变化 及其邻近的牵开器（骨骼）肌。这些区域基础 差异可以与交感神经系统中的相应差异相关联。 神经支配和/或细胞层内和细胞层之间的间隙连接表达。 将研究来自颊囊和牵开器的小动脉和供血动脉， 体内和体外。具体目标是确定：1）EC的作用， SMC作为传导通路; 2）EC和SMC之间的耦合性质 交感神经支配和缝隙连接的影响 表达对进行的血管反应。微量移液器提供刺激， 选择性地作用于SMC或EC，并用染料标记进行细胞内记录 解决SMC和EC特定信令事件。选择性破坏EC或 SMC信号传导是通过光染料损伤和药理学作用实现的。 干预结果将EC和SMC层的角色定义为 信号通路，定义的性质（化学和/或电） EC和SMC层之间的通信，并将链接的决定因素， 神经支配和缝隙连接区域性差异的传导 表情这些发现将提供深入了解如何控制 微血管阻力在结构不同的组织之间可能不同， 功能此外，区分SMC和EC在启动中的作用， 以及控制血流的血管中血管反应的传导， 上皮细胞和骨骼肌将有助于理解 组织灌注在诸如动脉粥样硬化的情况下受到损害， 糖尿病、高血压和局部缺血。

DESCRIPTION: (Adapted from the Investigator's Abstract): The long-term goal of this project is to define the cellular and molecular mechanisms that govern the integration and coordination of blood flow control. Electrical and vasomotor responses are conducted rapidly along arterioles and feed arteries to coordinate vasodilation and vasoconstriction in resistance networks. The working hypothesis is that conduction reflects the transmission of hyperpolarization (dilation) or depolarization (constriction) through gap junctions between endothelial cells (EC) and between smooth muscle cells (SMC) that comprise the vessel wall. The role of EC and SMC layers in conduction is unclear, as is the nature of coupling between respective layers. Further, conduction varies between microvessels of the epithelial hamster cheek pouch and its contiguous retractor (skeletal) muscle. The basis of these regional differences may be associated with corresponding differences in sympathetic innervation and/or gap junction expression within and between cell layers. Arterioles and feed arteries from cheek pouch and retractor will be studied in vivo and in vitro. The specific aims are to determine: 1) the role of EC and SMC as conduction pathways; 2) the nature of coupling between EC and SMC layers; and 3) the influence of sympathetic innervation and gap junction expression on conducted vasomotor responses. Micropipettes deliver stimuli that act selectively on SMC or on EC, and intracellular recording with dye labeling resolves SMC and EC specific signaling events. Selective disruption of EC or SMC signaling is achieved through light dye damage and pharmacological intervention. The results will define the roles of EC and SMC layers as signaling pathways, define the nature (chemical and/or electrical) of communication between EC and SMC layers, and will link the determinants of conduction with regional differences in innervation and gap junction expression. These findings will provide insight into how the control of microvascular resistance may vary between tissues that differ in structure and function. In addition, distinguishing the roles of SMC and EC in the initiation and conduction of vasomotor responses in vessels that control blood flow to epithelium and skeletal muscle will contribute to the understanding of how tissue perfusion is compromised in conditions such as atherosclerosis, diabetes, hypertension, and ischemia.