MECHANICS OF INTRAPULMONARY AIRWAY SMOOTH MUSCLE

该提案的目标是描述基本的机械特性 肺内气道平滑肌的性质。 无源和有源 两种圆柱段的张力-周长关系 将从正常大鼠分离的肺内支气管和细支气管 测定 将完成气道的形态测定分析， 测定管壁面积、平滑肌横截面积、 以及平滑肌细胞之间的联系 大大小小的 将通过计算活性细胞来比较气道收缩能力 应力使用测量的张力和平滑肌面积。 内容和 将测定收缩蛋白质，肌动蛋白和肌球蛋白的比例， 定量凝胶电泳检测呼吸道中。 评估气道 平滑肌作为负荷函数缩短的能力 在无负载下，力-速度关系和Vmax将为： 测定 药物反应性的依赖性 气道平滑肌细胞长度将通过比较 氨甲酰甲胆碱和异丙肾上腺素的浓度-反应关系. 三个圆周。 为了直接评估机械 平滑肌细胞的特性，我们将开发一个孤立的单一的 气道平滑肌细胞的制备及其被动和主动测定 长度-张力关系和力-速度特性。 这些 实验将是第一个详细的力学分析， 支气管和细支气管平滑肌的特性。 一个 了解正常气道中的这些特性将有助于 阻塞性肺疾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.