HYPOXIC PULMONARY VASOCANSTRICTION AND RED BLOOD CELLS

缺氧性肺血管收缩和红细胞

• 批准号: 2857562
• 负责人: STEVEN A DEEM
• 金额: $ 11.5万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2857562
• 关键词: adenosine; adenosine triphosphate; blood viscosity; erythrocytes; hemoglobin; high performance liquid chromatography; laboratory rabbit; luminescence; nitric oxide; perfusion; photolysis; pulmonary artery; purinergic receptor; receptor expression; respiratory gas; respiratory gas level; respiratory hypoxia; vascular endothelium; vasoconstriction

DESCRIPTION (Adapted from applicants' abstract) There is evidence that nitric oxide (NO) is important in red blood cell (RBC)-mediated modulation of hypoxic pulmonary vasoconstriction (HPV). NO may be involved directly in this modulation, or may act indirectly through its combination with hemoglobin (Hb) to form S-nitrosohemoglobin (SNO-Hb). In addition, the purines adenosine and adenosine triphosphate (ATP) may play a role in modulation of pulmonary vascular tone by RBCs. The interactions between RBCs and HPV are clinically relevant because of the common coexistence of anemia and pulmonary disease in critically ill patients. The specific aims of this project are: 1. To determine the effects of manipulation of NO production and metabolism or exogenously administered NO on pulmonary vascular tone during normoxia and hypoxia. 2. To distinguish between the roles played by the intact RBC and its constituent Hb alone in NO metabolism and modulation of HPV, and to determine the potential role of SNO-Hb in modulation of pulmonary vascular tone. 3. To measure pulmonary artery endothelial cell production of NO in a closed system, and to determine the effects of hypoxia and RBCs on endothelial NO production. 4. To elucidate the role of RBCs in purinergic modulation of pulmonary vascular tone by blocking uptake of adenosine by RBCs, by blocking purine receptors, and by assaying purinergic mediator production under normoxic and hypoxic conditions. 5. To determine whether purines affect release of NO by pulmonary artery endothelial cells in a closed system. These aims will be investigated using an isolated, perfused rabbit lung model with quantitiation of HPV done during repeated hypoxic gas challenges at different hematocrits, and with a cultured pulmonary artery endothelial cell model. Mediators will be assayed using chemiluminescence for measurement of expired NO and NO metabolites in perfusate, photolysis chemiluminescence for measurement of SNO-Hb, and high pressure liquid chromatography for measurement of purines in perfusate.

描述 （改编自申请人的摘要）有证据表明一氧化氮（NO） 在红细胞 (RBC) 介导的缺氧调节中很重要 肺血管收缩（HPV）。 NO可能直接参与此事 调节，或可能通过与血红蛋白结合间接发挥作用 (Hb) 形成 S-亚硝基血红蛋白 (SNO-Hb)。 此外，嘌呤 腺苷和三磷酸腺苷 (ATP) 可能在调节中发挥作用 红细胞的肺血管张力。 红细胞和 HPV 之间的相互作用是 由于贫血和贫血常见共存，因此具有临床相关性 重症患者的肺部疾病。 本次活动的具体目标 项目有： 1. 确定控制 NO 产生的效果 代谢或外源性NO对肺血管张力的影响 常氧和缺氧期间。 2. 区分角色 完整的红细胞及其成分 Hb 单独参与 NO 代谢和调节 HPV，并确定 SNO-Hb 在调节中的潜在作用 肺血管张力。 3. 测量肺动脉内皮细胞 在封闭系统中产生 NO，并确定缺氧的影响 和红细胞对内皮NO产生的影响。 4. 阐明红细胞在 通过阻断嘌呤能的摄取来调节肺血管张力 通过红细胞、阻断嘌呤受体以及测定嘌呤能来检测腺苷 常氧和低氧条件下介质的产生。 5. 确定 嘌呤是否影响肺动脉内皮细胞释放NO 在一个封闭的系统中。 这些目标将使用孤立的、 兔灌注肺模型，在重复过程中进行 HPV 定量 不同血细胞比容下的低氧气体挑战，以及培养 肺动脉内皮细胞模型。 将使用以下方法对介体进行测定 化学发光法测量过期 NO 和 NO 代谢物 灌注液、光解化学发光法测量 SNO-Hb 和高浓度 压力液相色谱法用于测量灌注液中的嘌呤。