EPITHELIUM AND BRONCHIAL REACTIVITY

首席研究员和他的同事们的早期工作 表明去除支气管上皮会导致 犬气道平滑肌高反应性 的 拟议研究的主要目标是：（a）继续 定义了上皮细胞调节的程度， 健康和疾病时气道平滑肌的反应性 （哮喘）;（B）确定支气管活性化合物的身份， 由上皮细胞分泌的因子;以及（c）开始探索 上皮和肺血管之间的相互作用。 将对犬和豚鼠的组织进行全程研究 预计五年期;某些实验将 在绵羊和人的材料上进行（如可用）。 的 所提出的方法主要涉及生理（测量 收缩反应，生物测定研究，电生理学 研究）和药理学研究，虽然在某些系列中， 生物化学（测量花生四烯酸的代谢物， 环核苷酸水平）和组织学测定将 被prfomred。 预计拟议的研究将 增加我们对影响支气管炎的因素的了解 语气，特别是提高我们的相互作用的知识， 在支气管壁的不同细胞之间， 中观察到的气道反应性增加的作用， 阻塞性肺病和支气管哮喘。 的研究 肺血管应该有助于解释 肺血管反应性可能会导致肺动脉收缩功能的改变， 通气灌注比，并可能提供一个解释 缺氧性肺血管收缩

Earlier work by the principal investigator and his associates has demonstrated that the removal of the bronchial epithelium causes hyperresponsiveness of canine airway smooth muscle. The principal goals of the proposed research are: (a) to continue to define the extent of the modulation by the epithelium of the responsiveness of airway smooth muscle in health and disease (asthma); (b) to determine the identity of the bronchoactive factors secreted by the epithelial cells; and (c) to start to explore interactions between epithelium and pulmonary blood vessels. Tissues of the dog and the guinea-pig will be studied throughout the projected five year period; certain experiments will be performed on material from sheep and humans (as available). The proposed approach involves mainly physiological (measurement of contractile responses, bioassay studies, electrophysiological studies) and pharmacological studies, although in certain series biochemical (measurement of metabolites of arachidonic acid, levels of cyclic nucleotides) and histological determinations will be prfomred. It is expected that the proposed research will increase our understanding of the factors which affect bronchial tone, and in particular improve our knowledge of the interactions between the different cells in the bronchial wall which can play a role in the increased reactivity of the airways observed in obstructive lung disease and bronchial asthma. The studies on pulmonary blood vessels should help to explain how changes in pulmonary vascular responsiveness may lead to alterations in the ventilation-perfusion ratio, and possibly provide an explanation for hypoxic pulmonary vasoconstriction.