ONTOGENY OF AIRWAY SMOOTH MUSCLE FUNCTION

气道平滑肌功能的个体发育

• 批准号: 3473253
• 负责人: KENNETH T NAKAMURA
• 金额: $ 7.71万
• 依托单位: KAPI'OLANI MEDICAL CENTER/WOMEN/CHILDRN
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473253
• 关键词: acetylcholine; beta adrenergic agent; bronchus; calcium channel blockers; controlled environment; cyclic AMP; cyclic GMP; gestational age; growth /development; guinea pigs; histamine; histology; hyperoxia; mature animal; muscle contraction; muscle function; muscle relaxants; newborn animals; perfusion; premature infant animal; respiratory distress syndrome of newborn; respiratory epithelium; smooth muscle; statistics /biometry; trachea

Neonatal respiratory distress syndrome (RDS) may be complicated by a forma of unresolved lung injury referred to as bronchopulmonary dysplasia (BPD). Treatment of RDS is believed to be partially responsible for the emergence of BPD by mechanisms such as oxygen toxicity. Many studies suggest that BPD is characterized in part by reactive airway disease in addition to lung parenchymal damage. On the other hand, while bronchodilators are frequently employed in the routine management of these infants, other studies suggest that large-airway collapse may complicate BPD and that bronchodilators may at times worsen airway obstruction by promoting large airway relaxation. Thus, abnormal airway smooth muscle tone probably plays an important role in the symptoms of BPD. Herein are described studies on isolated airway smooth muscle from 6 groups of guinea pigs: 1) term newborns between 1-3 days of age, randomized to breathe room air for 2-3 days; 2) or to breathe 95% oxygen for 2-3 days; 3) 6 week old adults (controls); 4) 6 week old adults that have been exposed to 95% oxygen in the newborn period for 2-3 days; 5) preterm newborns delivered 3-6 days prior to term and allowed to breathe room air; and 6)preterm newborns exposed to 95% oxygen as described for groups #2. These experiments will first define the normal ontogeny of airway smooth muscle responses to physiologic and pharmacologic stimuli in order to test the overall hypothesis that exposure to high oxygen concentrations during the newborn period alters the normal developmental pregression of airway smooth muscle function. The technique of isometric force measurements on segments of tracheal and bronchial rings will be employed to determine the following specific aims: 1) Determine if the normal ontogeny of airway smooth muscle response sis altered after exposure to high oxygen concentrations during the newborn period to physiologic, pharmacologic and environmental stimuli; 2) Determine if the effect of airway epithelial function during normal development changes after high oxygen exposure during the newborn period; 3) Determine if gestational age at birth influences airway smooth muscle reactivity following exposure to high oxygen concentrations; and 4) Determine if relaxation responses mediated by cAMP and cGMP correlate with measurements of intracellular cAMP and cGMP accumulation. The importance of these studies is best expressed by a recent NHLBI workshop summary on "Postnatal lung development in health and disease" that recommended that the "sequence of events leading to the early development of chronic lung diseases in neonates, . . . needs to be defined. The relative importance of oxygen toxicity, . . . and airway reactivity as etiologic factors in this disease process must be examined." (30). Thus, results of studies proposed herein hold the promise of achieving new knowledge that the NHLBI feel should be "given the highest priority" (30).

新生儿呼吸窘迫综合征(RDS)可能由一种形式并发 未解决的肺损伤称为支气管肺发育不良(BPD)。 对RDS的治疗被认为是出现RDS的部分原因 BPD的作用机制，如氧毒性。许多研究表明， 除肺外，BPD的部分特征是反应性呼吸道疾病。 实质损伤。另一方面，虽然支气管扩张剂 经常受雇于这些婴儿的日常管理，其他 研究表明，大气道塌陷可能会使BPD复杂化，而且 支气管扩张剂有时可能通过促进大剂量的 呼吸道松弛。因此，异常的气道平滑肌张力可能起作用。 在BPD的症状中起着重要作用。在此描述了关于 6组豚鼠的离体气道平滑肌：1)术语 出生1-3天的新生儿，随机呼吸室内空气2-3天 天；2)或呼吸95%氧气2-3天；3)6周龄成人 (对照)；4)暴露在空气中95%氧气的6周龄成人 新生儿期2-3天；5)早产儿分娩3-6天 未足月并允许呼吸室内空气；6)早产儿 暴露在95%的氧气中，如第二组所述。这些实验将 首先定义正常个体发育的气道平滑肌反应 生理和药物刺激，以测试总体 假设新生儿在出生期间暴露在高浓度氧气中 周期改变呼吸道平滑肌的正常发育进程 功能。节段等轴向力的测量技术 将使用气管和支气管环来确定以下各项 具体目的：1)确定正常的气道平滑肌个体发生 暴露在高氧浓度下的反应会发生改变 新生儿期对生理、药物和环境刺激的反应； 2)确定正常情况下对呼吸道上皮功能的影响 新生儿期高氧暴露后发育变化； 3)确定出生时的胎龄是否会影响呼吸道平滑肌 暴露在高氧浓度下的反应性；以及4) 确定cAMP和cGMP介导的松弛反应是否与 细胞内cAMP和cGMP积聚的测定。它的重要性 这些研究中最好的表述是最近NHLBI研讨会关于 “健康和疾病中的出生后肺发育”，建议 导致慢性肺早期发展的一系列事件 新生儿的疾病，。。。需要定义。它的相对重要性 氧气中毒，。。。和呼吸道反应性作为致病因素 这个疾病的过程必须被检查。“(30)。因此，研究结果 在此提出的承诺是实现新的知识，即NHLBI 感觉应该被“给予最高的优先权”(30)。