MATURATIONAL CORRELATES OF AIRWAY CONTRACTION

气道收缩的成熟相关性

• 批准号: 3349910
• 负责人: ALAN Richard LEFF
• 金额: $ 24.04万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1992-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349910
• 关键词: adenosinetriphosphatase; adrenergic receptor; asthma; autoradiography; bronchomotion; bronchospasm; growth /development; infant animal; innervation; isozymes; mature animal; muscle contraction; myosins; neural information processing; nicotinic receptors; respiratory airway pressure; respiratory function; respiratory muscles; respiratory pharmacology; sheep; smooth muscle; swine; trachea; vagotomy

Investigations are proposed to define mechanisms accounting for the topographical and maturational changes in airway contractile response elucidated in the prior grant period. Those studies demonstrated a heterogeneous distribution of bronchoconstrictor responses in the major resistance airways of dogs that were related to intrinsic differences in 1) mechanical properties of airways in situ, 2) differences in force of smooth muscle contraction, and 3) intrinsic stability and Laplacian characteristics of the airways in vivo. Studies of isolated airway muscle in vitro revealed substantial differences among airway generations in the force of isometric contraction, which was not related solely to topographical distribution of airway receptors. In preliminary studies during the prior grant period, methods have been developed for computerized morphometric analysis of airway muscle that allow for quantitative determination and assessment of the geometric distribution of airway constrictor forces in vivo. Techniques were developed for radioligand assays permitting assessment of the distribution of receptors in the various airway generations. A major extension of the previous work has been the application of these techniques to the study of the maturational responses of airway smooth muscle in swine. Because of the rapid maturation of this species, major alterations in airway muscle function may be demonstrated in brief time. An in situ isometric preparation was developed that permitted the comparative assessment of tracheal smooth muscle contractile forces of infant (2 week) and juvenile (8-12 week) swine. Substantial alterations in the mechanical and pharmacological properties of this muscle appear to occur with age. In vitro study of tracheal muscle from the same animals suggests substantial alterations in the contractile properties of porcine airway muscle with maturation. We propose to extend these studies further to 1) describe the in situ distribution of airway contractile response in situ (using tantalum bronchography), 2) the morphometric and biochemical changes occurring with maturation, and 3) the biophysical changes that occur in the various airway generations with maturation (using recently developed techniques for measurement of force-velocity and isometric contractile properties in bronchial airways). These mechanisms accounting for topographical and maturation differences in force of, smooth muscle contraction further will be elucidated through in vitro studies of 1) specific receptor ligands (with autoradiographic localization). 2) myosin isoenzymes and content, 3) rate of ATPase-myosin cross bridge cycling These investigations will employ an intradisciplinary approach to elucidate the morphometric, biophysical and biochemical correlates of airway contractility as they are developed both topographically and during maturation. These data should suggest basic physiological and pathophysiological differences that occur in airways during maturation and possible essential differences in therapeutic approaches between adult and pediatric reactive airway disease.

建议进行调查以确定机制 气道收缩的地形和成熟变化 先前拨款期间阐明的回应。那些研究 表现出支气管收缩剂的不均匀分布 相关狗的主要阻力气道的反应 1) 气道机械特性的内在差异 原位，2) 平滑肌收缩力的差异，以及 3) 气道的内在稳定性和拉普拉斯特征 体内。 离体气道肌的体外研究表明 各代气道的力量存在显着差异 等长收缩，这不仅仅与 气道受体的地形分布。 在初步 在之前的资助期间进行的研究，已经制定了方法 用于气道肌肉的计算机形态测量分析，允许 用于几何形状的定量测定和评估 体内气道收缩力的分布。 技术是 为放射性配体测定而开发，允许评估 受体在各代气道中的分布。 一个 先前工作的主要延伸是应用 这些技术用于研究成熟反应 猪气道平滑肌。 由于快速成熟 这个物种，气道肌肉功能的主要改变可能是 在短时间内展现出来。 原位等距制备是 开发允许对气管进行比较评估 婴儿（2周）和青少年的平滑肌收缩力 （8-12 周）猪。 机械和机械方面的重大改变 这种肌肉的药理学特性似乎随着年龄的增长而发生。 对同一动物气管肌肉的体外研究表明 猪的收缩特性发生重大改变 气道肌肉成熟。 我们建议扩大这些研究 进一步 1) 描述气道的原位分布 原位收缩反应（使用钽支气管造影），2） 成熟过程中发生的形态和生化变化，以及 3）各气道发生的生物物理变化 成熟的世代（使用最近开发的技术 用于测量力-速度和等长收缩 支气管气道的特性）。 这些机制占 平滑肌力量的地形和成熟差异 收缩将通过体外研究进一步阐明 1) 特异性受体配体（具有放射自显影定位）。 2) 肌球蛋白同工酶及含量，3) ATPase-肌球蛋白交叉率 桥式自行车 这些调查将采用 跨学科方法来阐明形态测量， 气道收缩力的生物物理和生化相关性 它们是在地形上和成熟过程中发育的。 这些数据应表明基本的生理和 气道中发生的病理生理学差异 成熟度和治疗上可能存在的本质差异 成人和儿童反应性气道疾病之间的方法。