EPITHELIUM AND BRONCHIAL REACTIVITY

首席调查员和他的同事们早先的工作 证明了去除支气管上皮会导致 犬呼吸道平滑肌的高反应性。这个 拟议研究的主要目标是：(A)继续 确定细胞上皮细胞调节的程度。 健康和疾病患者呼吸道平滑肌的反应性 (哮喘)；(B)确定支气管活动者的身份 上皮细胞分泌的因子；及(C)开始探索 上皮细胞与肺血管之间的相互作用。 狗和豚鼠的组织将在整个过程中进行研究。 预计的五年期间；某些试验将 对来自绵羊和人类的材料(如有)执行。这个 建议的方法主要涉及生理学(测量 收缩反应、生物测定研究、电生理 研究)和药理学研究，尽管是某些系列 生物化学(花生四烯酸代谢产物的测定， 环核苷酸水平)和组织学测定 会被冒犯的。预计拟议的研究将 加深对影响支气管因素的认识 语气，特别是提高了我们对相互作用的了解 在支气管壁中的不同细胞之间可以发挥作用 在观察到的呼吸道反应性增加中的作用 阻塞性肺病和哮喘。关于中国农业发展的研究 肺血管应该有助于解释 肺血管反应性可能导致肺功能的改变 通风-灌流比，并可能提供一种解释 用于缺氧性肺血管收缩。

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.