INTERCELLULAR COORDINATION OF BLOOD FLOW CONTROL

血管运动反应，在小动脉上的离散位置被触发 微管释放乙酰胆碱(ACh；扩张)、去甲肾上腺素(NE； 收缩)或KCI(收缩)是在以下距离内进行的 包括几毫米和多个分支。出现传导现象 组织血流局部控制的组成部分；进行的(但不是 局部)血管扩张增加微血管灌注量并减弱 交感神经血管收缩。然而，背后的信号(S) 传导是未知的。我们的工作假设是传导 血管舒缩反应反映了细胞膜变化的触发 沿小动脉壁在细胞间扩散的电位(Em)， 通过“机电”耦合产生的I直径响应。最重要的是 脑血管舒缩活动与电事件之间的对应关系 构成小动脉的细胞尚未确定。因此，用仓鼠 易于细胞内微电极进入的面颊袋制备 对于活体小动脉，我们的首要目标是确定它们之间的关系 在规定的刺激浓度下，Em和微动脉直径之间的关系 ACh、NE和KCI的累积剂量-反应曲线；硝普钠(NP)， 不诱导传导的扩张器也将被评估。这些 实验将从根本上为我们提供关于 机电耦合与药物-机械耦合在控制运动中的作用 微动脉阻力。我们的第二个目标是研究细胞内 与血管扩张和传导相对应的事件 小动脉网络中的血管收缩。ACH、NP、NE和KCI将是 将微管应用于定义的微动脉网络中的特定部位 在建立时同时测量Em和微动脉直径 与刺激部位的传导距离(500至1500微米)。这些 实验将确定细胞之间的电信号在 血管运动反应的传导。而同源缝隙连接 内皮细胞和内皮细胞之间的偶联被清楚地证明。 血管内皮细胞和平滑细胞之间的异源偶联 肌肉细胞仍然存在争议。微量注射荧光黄的应用 在记录过程中，我们的第三个目标是确定 内皮细胞和平滑肌细胞特异的反应 与血管扩张和收缩的启动和传导有关。我们的 长期目标是了解细胞间通信在 协调组织血流的局部控制。最新的知识 血管细胞生理学在很大程度上是基于培养和分离 血管准备。虽然这些模型提供了有价值的 信息，这是至关重要的流动控制的细胞机制 在活体微循环中进行研究。来自这些的发现 实验将为网络的动态控制提供独特的见解 并将被用来开发一种新的基础，从 关于疾病患者微血管病理生理学的测试假说 条件。

Vasomotor responses, triggered at discrete locations on arterioles by micropipet release of acetylcholine (ACh; dilation), norepinephrine (NE; constriction), or KCI (constriction), are conducted over distances which encompass several millimeters and multiple branches. Conduction appears integral to the local control of tissue blood flow; conducted (but not localized) vasodilation increases microvascular perfusion and attenuates sympathetic vasoconstriction. Nevertheless, the signal(s) which underlie conduction are unknown. Our working hypothesis is that conduction of vasomotor responses reflects the triggering of a change in membrane potential (Em) which spreads cell-to-cell along the arteriolar wall, resulting i diameter responses via 'electromechanical' coupling. Foremost, the correspondence between vasomotor activity and electrical events in the cells which comprise arterioles is undefined. Therefore, using he hamster cheek pouch preparation to facilitate intracellular microelectrode access to arterioles in vivo, our First Aim is to determine the relationship between Em and arteriole diameter at defined stimulus concentrations during cumulative dose-response curves to ACh, NE, and KCI; nitroprusside (NP), a dilator which does not induce conduction, will also be evaluated. These experiments will provide fundamentally new insight into the sole of electromechanical vs. pharmacomechanical coupling in the control of arteriole resistance. Our Second Aim is to investigate the intracellular events which correspond to the conduction of vasodilation and vasoconstriction in arteriole networks. ACh, NP, NE, and KCI will be applied with micropipets to specific site in defined arteriole networks while measuring Em and arteriole diameter simultaneously at established conduction distances (500 to 1500 mum) from the stimulus site. These experiments will define the role of electrical signaling between cells in the conduction of vasomotor responses. Whereas homologous gap-junctional coupling is clearly demonstrated between endothelial cells and between smooth muscle cells,, heterologous coupling between endothelial and smooth muscle cells remains controversial. Using microinjection of Lucifer Yellow dye to label cells during recording, our Third Aim is to determine endothelial cell-and smooth muscle cell-specific responses which correspond to the initiation and conduction of vasodilation and vasoconstriction. Our long-term goal is to understand the role of cell-to-cell communication in coordinating the local control of tissue blood flow. Current knowledge of vascular cell physiology is based largely upon cultured and isolated vascular preparations. While such models have provided valuable information, it is essential that cellular mechanisms of flow control be investigated in the living microcirculation. Findings from these experiments will provide unique insight into the dynamic control of network resistance and will be used to develop a novel foundation from which to test hypotheses regarding microvascular pathophysiology in diseased conditions.