REGULATION OF MICROVASCULAR PERMEABILITY BY NITRIC OXIDE

描述 (摘自申请者的摘要)本申请书为临床导师 科学家发展奖旨在为首席研究员提供 (P.I.)，伦博博士，发展所需的研究经验和技能 成为一名独立的调查员。私家侦探是一名助理教授 密苏里大学肺部/重症监护科。他的 该司的临床和教学职责将占20% 他的全部时间努力。该部门有一个积极的临床研究计划， 重点是与两种疾病有关的主要变化 微血管功能、脓毒症和急性呼吸窘迫综合征 (ARDS)。私家侦探正在攻读生理学博士学位。 弗吉尼亚·赫胥黎博士的指导和指导。的环境 心血管研究和细胞传输非常出色，85%的 生理系在这一领域开展工作。 该研究计划将研究一氧化氮(NO)在调节中的作用 微血管对水和溶质的渗透性。微血管 渗透性是调节水和溶质交换的动态过程， 并且可以通过各种刺激从基础水平增加或降低。 NO是一种内皮衍生的松弛因子，它参与了 调节局部血流和压力。一氧化氮对人体健康的影响 微血管通透性的调节尚不清楚，因为增加和 已经描述了NO合成酶抑制剂对交换的减少。这个 这一应用的中心假设是基础NO释放调节 微血管对水和溶质的渗透性。此应用程序将 联合应用四种评估微血管交换的方法 活体大鼠肠系膜小静脉，以检验两个假说：1)基础释放 一氧化氮影响基础静脉对水和溶质的通透性，以及 2)循环体液和/或细胞因素导致 血管蛋白渗漏受一氧化氮合酶抑制。这样做的长期目标是 研究旨在阐明微血管通透性的机制 是在生理条件下调节的。这将为我们提供对 与血管紧张素转换有关的疾病的病理生理学 微血管通透性，如脓毒症和ARDS，可能会产生 微血管功能障碍更合理的药理学研究 存在于这些和其他疾病实体中。(摘要结束)

DESCRIPTION (Adapted from applicant's abstract) This application for a mentored clinical scientist development award is designed to offer the principal investigator (P.I.), Dr. Rumbaut, the necessary research experience and skills to develop into an independent investigator. The P.I. is an Assistant Professor in the Pulmonary/Critical Care Division of the University of Missouri. His clinical and teaching responsibilities in the Division will comprise 20% of his full time effort. The Division has an active clinical research program, with an emphasis on two diseases associated with major alterations in microvascular function, sepsis and acute respiratory distress syndrome (ARDS). The P.I. is enrolled in a doctoral program in Physiology, under the mentorship and guidance of Dr. Virginia Huxley. The environment for cardiovascular research and cellular transport is excellent, as 85% of the physiology department works in this area. The research plan will examine the role of nitric oxide (NO) on regulation of microvascular permeability to water and solutes. Microvascular permeability is a dynamic process which regulates water and solute exchange, and may be increased or decreased from basal levels by a variety of stimuli. NO is an endothelial-derived relaxing factor which participates in regulation of local blood flow and pressure. The influence of NO on regulation of microvascular permeability is unclear, as both increases and decreases in exchange by NO synthase inhibitors have been described. The central hypothesis of this application is that basal NO release regulates microvascular permeability to water and solutes. This application will combine four methodologies of assessment of microvascular exchange in in vivo rat mesenteric venules, to test two hypotheses: 1) Basal release of nitric oxide influences basal venular permeability to water and solutes, and 2) Circulating humoral and/or cellular factors account for the increases in vascular protein leakage by NOS inhibition. The long term goal of this research is to elucidate the mechanisms by which microvascular permeability is regulated under physiologic conditions. This will provide insight into the pathophysiology of diseases which are associated with alterations in microvascular permeability, such as sepsis and ARDS, and will likely yield a more rational pharmacological approach to the microvascular dysfunction present in these and other disease entities. (End of Abstract)