MECHANICS OF INTRAPULMONARY AIRWAY SMOOTH MUSCLE

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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.