MECHANICS OF INTRAPULMONARY AIRWAY SMOOTH MUSCLE

这项提案的目标是描述基本的机械 肺内气道平滑肌的特性。被动与主动 两种圆柱体节段的拉力-周长关系 从正常大鼠肺内分离的支气管和细支气管会 下定决心。将完成对呼吸道的形态分析，以 测定室壁面积、平滑肌横截面积、方位 以及平滑肌细胞之间的连接。大大小小的 通过计算活性细胞来比较呼吸道收缩能力 使用测量的张力和平滑肌面积来施加应力。内容和 收缩蛋白，肌动蛋白和肌球蛋白的比例将被确定。 通过定量凝胶电泳法在呼吸道中检测到。评估呼吸道状况 作为负荷的函数和最大限度地缩短平滑肌的能力 在空载下，力-速度关系和Vmax将是 下定决心。阿司匹林的药理反应依赖性 气道上的平滑肌细胞长度将通过比较 苯二酚和异丙肾上腺素的量效关系 三个圆周。为了直接评估机械设备 我们将开发一种分离的单个平滑肌细胞的性质 呼吸道平滑肌细胞的制备及其活性和被动性测定 长度-张力关系和力-速度特性。这些 实验将是第一次详细的力学分析 细支气管处和细支气管处的平滑肌的特性。一个 了解正常呼吸道中的这些特性将有助于 阻塞性肺病发病机制的未来研究。

The goal of this proposal is to characterize the basic mechanical properties of intrapulmonary airway smooth muscle. The passive and active tension-circumference relationships of cylindrical segments of both intrapulmonary bronchi and bronchioles isolated from normal rats will be determined. Morphometric analysis of the airways will be completed to determine wall area, smooth muscle cross-sectional area, the orientation and connections between the smooth muscle cells. The large and small airway contractile capability will be compared by calculating active cell stress using the measured tension and smooth muscle area. The content and the ratio of the contractile proteins, actin and myosin, will be determined in the airways by quantitative gel electrophoresis. To assess the airway smooth muscle's ability to shorten as a function of load and maximally under no load, the force-velocity relationship and Vmax will be determined. The dependence of the pharmacologic responsiveness of the airways on smooth muscle cell length will be determined by comparing the concentration-response relationships of bethanechol and isoproterenol at three circumferences. In order to directly assess the mechanical properties of the smooth muscle cells we will develop an isolated single airway smooth muscle cell preparation and determine its passive and active length-tension relationships and force-velocity characteristics. These experiments will be the first detailed mechanical analysis of the properties of the smooth muscle in bronchi and bronchioles. An understanding of these properties in the normal airway will be useful in future studies of the pathogenesis of obstructive lung disease.