REGULATION OF MICROVASCULAR PERMEABILITY BY NITRIC OXIDE

描述 （改编自申请人摘要）本申请指导临床 科学家发展奖旨在为首席研究员提供 （P.I.），Rumbaut博士，必要的研究经验和技能， 独立调查员 私家侦探是一个助理教授在 密苏里州大学肺/重症监护部。 他 该科的临床和教学职责将占20%， 他的全部时间的努力。 该部门有一个积极的临床研究计划， 重点是两种疾病， 微血管功能、脓毒症和急性呼吸窘迫综合征 （ARDS）。 私家侦探在生理学博士课程就读，根据 弗吉尼亚·赫胥黎博士的指导 的环境 心血管研究和细胞运输是优秀的，因为85%的 生理学系在这方面的工作。 该研究计划将研究一氧化氮（NO）在调节 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减少。 NO是一种内皮源性舒张因子， 局部血流和血压的调节。 NO对 微血管通透性的调节尚不清楚，因为两者都增加， 已经描述了通过NO合酶抑制剂降低交换。 的 本申请的中心假设是基础NO释放调节 微血管对水和溶质的渗透性。 此应用程序将 联合收割机评估微血管交换的四种方法 体内大鼠肠系膜微静脉，以测试两个假设：1）基础释放的 一氧化氮影响基底微静脉对水和溶质的渗透性， 2)循环的体液和/或细胞因子解释了 NOS抑制血管蛋白渗漏。 长期目标是 研究的目的是阐明微血管通透性 是在生理条件下调节的。 这将提供深入了解 疾病的病理生理学与改变有关， 微血管通透性，如脓毒症和ARDS，并可能产生一个 更合理的药物治疗微血管功能障碍 存在于这些和其他疾病实体中。 (End摘要）

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)