MATURATIONAL CORRELATES OF AIRWAY CONTRACTION

气道收缩的成熟相关性

• 批准号: 3349905
• 负责人: ALAN Richard LEFF
• 金额: $ 21.19万
• 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/3349905
• 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.

建议开展调查，以确定 气道收缩的地形和成熟变化 在前一个赠款期间阐明的答复。这些研究 表明支气管收缩剂的不均匀分布 犬的主要阻力气道的反应， 1）气道的机械特性， 原位，2）平滑肌收缩力的差异，以及3） 气道的固有稳定性和拉普拉斯特征 in vivo. 离体气道肌肉的研究显示， 气道各代之间的作用力存在实质性差异， 等长收缩，这不仅与 气道受体的地形分布。 初步 在前一个赠款期间的研究，方法已经制定 用于气道肌肉的计算机化形态测量分析， 用于定量测定和评估 气道收缩力在体内的分布。 技术被 开发用于放射性配体测定，以评估 受体在各代气道中的分布。 一 以前工作的主要扩展是应用 这些技术的成熟反应的研究， 猪的气道平滑肌。 由于快速成熟， 这种物种，气道肌肉功能的主要改变可能是 在短时间内演示。 原位等长制备， 开发了允许比较评估气管 婴儿（2周）和青少年平滑肌收缩力 (8-12周）猪。 在机械和 这种肌肉的药理学性质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， 猪的收缩特性的实质性改变 成熟的气道肌肉。 我们建议扩展这些研究 进一步描述气道的原位分布 原位收缩反应（使用钽支气管造影），2） 随着成熟发生的形态和生化变化，以及 3)在各种气道中发生的生物物理变化 成熟世代（使用最近开发的技术 用于测量力-速度和等长收缩 在支气管气道中的性质）。 这些机制占 平滑肌张力的地形和成熟差异 收缩将通过体外研究进一步阐明， 1)特异性受体配体（放射自显影定位）。 2)肌球蛋白同工酶及含量; 3）ATP酶-肌球蛋白杂交率 这些调查将采用 跨学科的方法来阐明形态， 生物物理和生物化学相关的气道收缩， 它们在地形上和成熟过程中发育。 这些数据应该表明基本的生理和 在呼吸道中发生的病理生理学差异， 成熟和治疗上可能的本质差异 成人和小儿反应性气道疾病之间的方法。