PULMONARY VASODILATION AND GUANYLATE CYCLASE REGULATION

为了更好地理解监管的作用 胞浆形式的鸟苷酸环化酶在调控中的作用 肺血管张力是这一长期目标 求婚。本文件中描述的研究的具体重点 应用是表征和确定潜力 肺血管调节的生理机制 涉及对鸟苷环化酶胞浆形式的调节，以及 产生一种细胞内血管介质的酶- 松弛，循环GMP。我们的研究将试图阐明 环状GMP相关机制的细节或调节 肌张力和胞浆鸟苷环化酶的调节 过氧化氢，内皮，氧分压的变化 以及暴露在阳光下。拟议研究的一个主要方面将是 致力于生理学的测定 胞浆激活的一种新机制及其意义 过氧化氢酶介导的鸟苷环化酶对过氧化氢的代谢 这是我们最近发现的。这些问题将是 在离体肺血管环和 未纯化的血管和纯化的鸟苷环化酶都得到了 从牛肺中提取。测量收缩能力的变化， 大鼠组织环GMP水平及鸟苷环化酶活性的变化 存在各种激动剂、拮抗剂和生成剂或 潜在调解人的拾荒者将被雇用来调查 并重建血管张力和血管张力的控制机制 鸟苷环化酶，并对所涉及的介体进行表征。 这些研究的结果将使我们能够更好地了解 肺气肿控制的重要生理机制 血管张力，并为旨在 确定它们在多种肺病发病机制中的作用 与肺动脉高压相关的血管疾病。

To provide a better understanding of the role of the regulation of the cytosolic form of guanylate cyclase in the control of pulmonary vascular tone is the long range objective of this proposal. The specific focus of the studies described in this application is to characterize and determine potential physiological mechanisms of pulmonary vascular regulation that involve modulation of the cytosolic form of guanylate cyclase, an enzyme which generates an intra-cellular mediator of vaso- relaxation, cyclic GMP. Our studies will attempt to elucidate the details of cyclic GMP associated mechanisms or modulation of smooth muscle tone and cytosolic guanylate cyclase regulation by hydrogen peroxide, the endothelium, changes in oxygen tension and exposure to light. A major aspect of the proposed studies will be directed toward the determination of the physiological significance of a new mechanism of activation of cytosolic guanylate cyclase by catalase mediated metabolism of peroxide that we have recently discovered. These problems will be investigated in isolated pulmonary vascular rings and with unpurified vascular and purified guanylate cyclase all obtained from bovine lungs. Measurements of changes in contractility, tissue cyclic GMP levels and guanylate cyclase activity in the presence of various agonists, antagonists and generators or scavengers of potential mediators will be employed to investigate and reconstruct the mechanisms of control of vascular tone and guanylate cyclase, and to characterize the mediators involved. Results of these studies will enable us to better understand some important physiological mechanisms of control of pulmonary vascular tone and provide the bsis for studies designed to determine their role in the pathogenesis of a variety of pulmonary vascular disorders related to pulmonary hypertension.