The Dynamics of Nitric Oxide in the Vascular System

一氧化氮在血管系统中的动态

• 批准号: 7070634
• 负责人: Jack R Lancaster
• 金额: $ 29.05万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7070634
• 关键词: blood vessels; cell wall; electrodes; erythrocytes; fluorescence spectrometry; human tissue; intermolecular interaction; laboratory rat; nitric oxide; oxygen tension; oxygen transport; tissue /cell culture; vascular endothelium; vascular smooth muscle; vasodilation

DESCRIPTION (provided by applicant): Although the endothelium-derived relaxing factor (EDRF) is generally acknowledged to be nitric oxide (including the Nobel committee, 1998), there is much uncertainty regarding the exact molecular identity of EDRF, specifically, whether it is free NO or a related nitrogen oxide species. Much of the reason for this uncertainty is due to the general perception that the dynamics of free NO are not suitable for its role as EDRF, specifically, that it is too short-lived. In this proposal, we will specifically examine this important issue, namely, we will identify and quantify the processes which determine the dynamics of NO in the vascular system. Our three Specific Aims are organized according to the three compartments involved: the vascular lumen, wall, ablumen. In Specific Aim I we will address the dynamics of NO in the lumen. Specifically, we hypothesize that the major process which defines NO dynamics in this compartment is the irreversible consumption of NO by oxyhemoglobin within the erythrocyte. Even though this represents the major sink for NO in vivo, this process is slow enough that free NO can still function as EDRF; we will delineate the origin for this retardation, which is due to encapsulation of oxyhemoglobin within the erythrocyte. We will also examine the kinetic competence of the formation of nitrosothiol-hemoglobin as a possible carrier of NO. In Specific Aim II we will test whether it is free NO which is the direct effector of vascular relaxation in the vessel wall. We will address this by testing the hypothesis that if it is free NO which is the messenger between the endothelial cell and the smooth muscle cell, then relaxation under a variety of conditions should directly correlate with the concentration of free NO (which we will measure directly with NO-specific electrodes). In Specific Aim III we will address the lifetime of NO in the perivascular region surrounding a vessel, and test whether in addition to causing vasodilation a second role for NO is to extend the distance that oxygen diffuses away from the vessel.

描述（由申请人提供）：尽管通常认为内皮细胞衍生的放松因子（EDRF）是一氧化氧化物（包括诺贝尔委员会，1998年），但对于EDRF的确切分子认同，特别是免费的，无论是免费的还是相关的氮氧化物。 这种不确定性的许多原因是由于普遍认为自由否的动态不适合其作为EDRF的作用，特别是它太短暂了。 在此提案中，我们将专门研究这个重要问题，即，我们将确定并量化确定血管系统中NO动态的过程。 我们的三个特定目标是根据所涉及的三个隔室组织的：血管腔，墙壁，阿布鲁人。 在特定的目的中，我将解决管腔中NO的动态。 具体而言，我们假设定义该隔室中NO动态的主要过程是红细胞内的氧气蛋白质对NO的不可逆转消耗。 即使这代表了不体内的主要水槽，但此过程足够缓慢，以至于免费无需作为EDRF工作。我们将描述这种迟缓的起源，这是由于红细胞内的氧降压蛋白的封装所致。 我们还将研究硝基硫醇 - 血红蛋白形成的动力学能力。 在特定的目标II中，我们将测试它是否是免费的，这是血管壁中血管松弛的直接效应器。 我们将通过测试以下假设来解决这一问题：如果它是自由的，那是内皮细胞和平滑肌细胞之间的使者，那么在各种条件下的放松应与自由NON的浓度直接相关（我们将用无特定电极直接测量）。 在特定的目标III中，我们将解决血管周围血管周围区域中NO的寿命，并测试除了引起血管舒张外，NO的第二个作用是否是延长氧气从血管扩散的距离。