INTERCELLULAR COMMUNICATION IN MICROVESSELS

小动脉壁内的细胞间信号传递提供了一个重要的联系 将单个血管平滑肌和内皮细胞连接成一个 功能性阻力容器，其可以作为 微循环化学信号传导（例如EDRF），生肌机制， 血流依赖性扩张和传导性血管扩张反应都是 涉案这些进程不仅有助于统一各组织的活动， 单个电池，而且还协调串联和并联元件 以确保血流的均匀分布 各种器官之间和内部的细胞和分子基础 进行的血管反应是研究最少的 的综合机制，我们的实验室已经进行了一项 多学科计划旨在纠正这一缺陷，并在 提供对疾病基本生理学和病理生理学的见解 血管壁讨论了两个广泛的问题。什么是细胞 导致传导的事件，以及参与传导的途径 传导？我们的工具包括：体外和体内全细胞电 除了电压敏感染料之外， 测量血管平滑肌的膜电位， 内皮细胞，钙敏感染料监测Ca++信号，染料 注射以追踪细胞连接，免疫组织化学以确定 血管壁和原位连接的解剖学途径 杂交以确定连接蛋白（GAP）的来源细胞 junctions）。我们建议将这些工具与细胞和 受体特异性激动剂、间隙连接解偶联剂和反义寡核苷酸， 寡核苷酸来测试六个关键假设。 L.膜电位的变化是必要的，也是充分的 传导性血管反应信号。 2. Ca+ +或其他第二信使的纵向扩散有助于 纵向沟通。 3.平滑肌或内皮可能参与a.）启动， 和B.）进行响应。 4.毛细血管内皮是连接毛细血管的传导通路 和小动脉。 5.差距连接提供了同细胞和异细胞途径 用于传导。 6.小动脉壁的细胞间传导系统处于 生理控制

Cell-cell signaling within the arteriolar wall provides a vital link uniting individual vascular smooth muscle and endothelial cells into a functional resistance vessel which can operate as a part of the microcirculation. Chemical signaling (e.g. EDRF), the myogenic mechanism, flow dependent dilation and the conducted vasomotor response are all involved. These processes serve not only to unify the activities of the individual cells, but also to coordinate the series and parallel elements of the vasculature so as to assure the uniform distribution of blood flow among and within the various organs The cellular and molecular bases of the conducted vasomotor response have been the least investigated of any of the integrative mechanisms, and our laboratory has undertaken a multidisciplinary program aimed at rectifying this deficit, and in providing insights into the basic physiology and pathophysiology of the vascular wall. Two broad questions are addressed. What are the cellular events leading to conduction, and what are the pathways involved in conduction? Our tools include: in vitro and in vivo whole-cell electrical recording from micropipettes in addition to voltage sensitive dyes for measurement of membrane potential of vascular smooth muscle and endothelial cells, calcium sensitive dyes to monitor Ca++ signaling, dye injection to trace cellular connectivity, immunohistochemistry to define the anatomical pathways of connectivity in the vessel wall, and in situ hybridization to determine the cells of origin for connexin proteins (gap junctions). We propose to use these tools in combination with cell and receptor specific agonists, gap junction uncouplers, and antisense oligonucleotides to test six critical hypotheses. l. A change in membrane potential is the necessary and the sufficient signal for conducted vasomotor response. 2. Longitudinal diffusion of Ca+ + or other second messenger contributes to longitudinal communication. 3. Either smooth muscle or endothelium may participate in a.) initiating, and b.) conducting the response. 4. The capillary endothelium is a conduction pathway uniting capillaries and arterioles. 5. The gap junctions provide both homocellular and heterocellular pathways for conduction. 6. The intercellular conduction system in the arteriolar wall is under physiological control.