Red Blood Cells, Nitric Oxide and Pulmonary Circulation

红细胞、一氧化氮和肺循环

• 批准号: 6911843
• 负责人: STEVEN A DEEM
• 金额: $ 9.86万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-26 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6911843
• 关键词: cell morphology; erythrocytes; hemodynamics; hemoglobin; hypoxia; intravital microscopy; laboratory rat; membrane transport proteins; microcirculation; nitric oxide; nitrites; perfusion; pulmonary circulation; respiratory gas transport; vasodilation; vasomotion

DESCRIPTION (provided by applicant): The long term objectives of this project are to elucidate the role of red blood cells (RBCs), hemoglobin (Hb), and nitric oxide (NO) in modulating pulmonary blood flow at the microvascular and macrovascular levels, and to thereby provide insight into the mechanisms by which RBCs affect pulmonary gas exchange. The knowledge gained from this project will have health-related ramifications, in that it will allow more informed understanding and treatment of anemia, a common accompaniment of illness, and ultimately lead to improvements in patient care through the optimization of transfusion strategies and the development of hemoglobin-based oxygen carriers. Dr. Deem has previously described the importance of RBCs in augmenting hypoxic pulmonary vasoconstriction through inactivation of NO by Hb, and has delineated the enhancement of pulmonary gas exchange by anemia under certain conditions. The current project will build on these findings in the following Specific Aims: I. Determine whether NO that is "biopreserved in the form of the oxidation product nitrite, or the NO-Hb products nitrosyl(heme)Hb and S-nitrosoHb can be released in the pulmonary circulation and result in vasodilation. The effect of these products on pulmonary artery pressure and NO production will be studied during normoxic and hypoxic conditions in an isolated, perfused rat lung model and in anesthetized rats. In addition, this aim will explore whether encapsulation of Hb within the red blood cell membrane alters the vasoactive properties of NO-Hb products. II. Determine the role of RBCs in determining microvascular hemodynamics using intravital microscopy in isolated, perfused rat lungs. This Aim will directly explore the rheology of the pulmonary microcirculation, help determine whether the RBC plays an active or passive role in determining pulmonary microvascular hemodynamics, and provide insights into the mechanisms by which RBCs alter pulmonary blood flow distribution and gas exchange.

描述（由申请人提供）： 该项目的长期目标是阐明红细胞（RBC）、血红蛋白（Hb）和一氧化氮（NO）在微血管和大血管水平调节肺血流中的作用，从而深入了解红细胞影响肺气体交换的机制。 从该项目中获得的知识将产生与健康相关的影响，因为它将让人们对贫血这种常见疾病有更深入的了解和治疗，并最终通过优化输血策略和开发基于血红蛋白的氧载体来改善患者护理。 Deem 博士之前曾描述过红细胞通过 Hb 灭活 NO 来增强缺氧性肺血管收缩的重要性，并描述了贫血在某些条件下增强肺气体交换的作用。当前的项目将基于这些发现，实现以下具体目标： I. 确定“以氧化产物亚硝酸盐或 NO-Hb 产物亚硝酰（血红素）Hb 和 S-亚硝基 Hb 形式生物保存的 NO 是否可以在肺循环中释放并导致血管舒张。这些产品对肺动脉压力和 NO 产生的影响将在隔离的常氧和缺氧条件下进行研究， 灌注大鼠肺模型和麻醉大鼠。此外，该目标还将探讨红细胞膜内 Hb 的封装是否会改变 NO-Hb 产品的血管活性特性。二.使用活体显微镜在离体、灌注的大鼠肺中确定红细胞在确定微血管血流动力学中的作用。该目的将直接探索肺微循环的流变学，帮助确定是否 红细胞在确定肺微血管血流动力学方面发挥着主动或被动的作用，并为红细胞改变肺血流分布和气体交换的机制提供了见解。