ROLE OF VASOACTIVE MEDIATORS IN PULMONARY CIRCULATING CO

血管活性介质在肺循环 CO 中的作用

• 批准号: 3082095
• 负责人: ROBYN J BARST
• 金额: $ 4.89万
• 依托单位: NEW YORK MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3082095
• 关键词: arachidonate; biological fluid transport; carbon dioxide tension; cardiac output; catecholamines; controlled environment chamber; eicosanoid metabolism; embryo /fetus hypoxia; human subject; hypoxia; kallikreins; mature animal; newborn animals; oxygen tension; prostacyclins; pulmonary circulation; pulmonary edema; pulmonary hypertension; radioimmunoassay; renin angiotensin system; respiratory pharmacology; thromboxanes; vascular endothelium permeability; vasoactive agent

The long-term goal is to pursue an academic career as an independent investigator, clinical consultant and teacher. The applicant plans to develop specific expertise in the area of the control of the pulmonary circulation, focusing on the role of vasoactive substances in the mediation of pulmonary vascular tone and pulmonary transvascular exchange of water and protein. This study will investigate the role of vaso-active substances in both human and animal models of pulmonary hypertension. Studies of the metabolic activities of the lung indicate that several mediator systems interact to produce net circulatory effects, especially in pathophysiologic states. Thus, the study of the interrelationships between the renin-angiotensin, kallikrein-kinin and catecholamine systems and the arachidonate cascade is a principal focus of this proposal since each of these systems is known to be vasoactive in the pulmonary circulation. Models of altered pulmonary function in chronically-instrumented, unanesthetized sheep and newborn lambs will include acute, chronic and repeated intermittent hypoxia (with and without hypercarbia) and pulmonary hypertention in the newborn (induced by intrauterine hypoxia). The specific aims are: 1. To examine the effects of changes in gas tension (PaO2, PaCO2, pH) on the endogenous activity of these mediator systems; 2. To relate these induced changes in mediator concentrations to changes in pulmonary and systemic hemodynamics (electromagnetic flow probe and thermodilution methods), pulmonary transvascular exchange of water and protein (endogenous proteins in lung lymph and plasma using electroimmunoassay), gas exchange (alveolar to arterial oxygen gradient) and distribution of cardiac output (microsphere mehod); 3. To use selective pharmacologic blockers and inhibitors to establish the relative contributions of these mediator systems to the observed ciculatory changes. Studies will be performed in patients with idiopathic pulmonary hypertension in the newborn (persistence of the fetal circulation) or older child, and pulmonary hypertension secondary to congenital heart defects or respiratory disorders. By focusing on the interactions between these vasoactive mediator systems, these studies will provide new insights into the pathogenesis of pulmonary hypertension and pulmonary edema, and suggest new approachs to pharmacologic intervention.

长期目标是从事独立的学术职业 研究人员，临床顾问和老师。 申请人计划 在控制肺部控制领域发展特定的专业知识 循环，专注于血管活性物质在调解中的作用 肺血管张力和肺部血管的水交换 和蛋白质。 这项研究将研究血管活性的作用 人类和动物模型中肺动脉高压的物质。 对肺的代谢活性的研究表明 中介系统相互作用以产生净循环效应，尤其是在 病理生理状态。 因此，研究 肾素 - 血管紧张素，kallikrein-kinin和Catecholamine Systems以及 Arachidonate Cascade是该提案的主要重点 已知这些系统在肺循环中具有血管活性。 慢性启发性肺功能改变的模型， 未经麻醉的绵羊和新生羔羊将包括急性，慢性和 反复间歇性缺氧（有和没有超碳化物）和肺部 新生儿的高血压（由宫内缺氧诱导）。 这 具体目的是：1。检查气体张力变化的影响 （PAO2，PACO2，pH）这些介体系统的内源性活性； 2。 将这些引起的介体浓度变化与变化联系起来 肺部和全身血流动力学（电磁流探针和 热稀释方法），水和水的肺经术交换 蛋白质（使用肺淋巴和血浆中的内源性蛋白使用 电免疫测定），气体交换（牙槽到动脉氧梯度） 和心输出量（微球MEHOD）的分布； 3。使用选择性 药理阻滞剂和抑制剂以建立相对 这些介体系统对观察到的丝网的贡献 更改。 将在特发性肺患者中进行研究 新生儿的高血压（胎儿循环的持续性）或年龄较大 儿童和继发于先天性心脏缺陷的肺动脉高压或 呼吸系统疾病。 通过关注这些之间的互动 血管活性调解器系统，这些研究将为您提供新的见解 肺动脉高压和肺水肿的发病机理，并建议 药理干预的新方法。