INTERCELLULAR COMMUNICATION IN MICROVESSELS

小动脉壁内的细胞-细胞信号提供了一个重要的联系 将单个血管平滑肌和内皮细胞联合成一个 功能性阻力血管，可作为 微循环。化学信号(如EDRF)，肌肉发生机制， 血流依赖性扩张和传导的血管舒缩反应 牵涉其中。这些进程不仅有助于统一联合国系统的活动 单个电池，也要协调串联和并联的元素 以确保血液流动的均匀分布 在不同器官之间和内部的细胞和分子基础 传导的血管舒缩反应在所有研究中是最少的 综合机制，我们的实验室已经进行了 旨在纠正这一赤字的多学科计划，以及在 提供对人的基本生理学和病理生理学的见解 血管壁。本文提出了两个广泛的问题。细胞是什么？ 导致传导的事件，以及涉及的通路是什么 传导？我们的工具包括：体外和体内全细胞电学 除了用于记录的电压敏感染料外，还可从微吸管记录 血管平滑肌细胞膜电位的测定及临床意义 内皮细胞，钙敏感染料，用于监测钙离子信号，染料 注射示踪细胞连接，免疫组织化学定义 血管壁和原位连通的解剖学途径 用杂交技术确定连接蛋白(GAP)的细胞来源 交叉点)。我们建议将这些工具与cell和 受体特异性激动剂、缝隙连接解偶联剂和反义 寡核苷酸来测试六个关键假设。 L：膜电位的改变是必要的，也是充分的 传导血管运动反应的信号。 2.钙离子或其他第二信使的纵向扩散 到纵向沟通。 3.血管内皮细胞或血管内皮细胞均可参与a。启动中， 和b.)进行响应。 4.毛细血管内皮细胞是连接毛细血管的传导通路 和小动脉。 5.缝隙连接同时提供同细胞和异质细胞途径 用于传导。 6.小动脉壁细胞间传导系统 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.