RENAL MICROVASCULAR FUNCTION IN AGED RATS

老年大鼠肾微血管功能

• 批准号: 6132483
• 负责人: Edward W Inscho
• 金额: $ 1.14万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6132483
• 关键词: acetylcholine; age difference; angiotensin II; animal old age; endothelin; hemodynamics; kidney function; laboratory rat; microcirculation; muscle cells; nitric oxide; perfusion; renal artery; tissue /cell culture; vascular resistance; vasodilators; vasomotion

This NIA Pilot Research Grant application (RO3) application is focused on directly examining renal microvascular function in the kidneys of aging animals for the purpose of establishing critical data on primary microvascular function and to obtain the essential preliminary data for preparation of a more comprehensive RO1 proposal in the coming year. Currently, no studies have directly examined renal microvascular function in aged animals yet reduced renal function is commonly associated with the age-related decline in physiologic cardiovascular homeostasis. Experiments will be performed in vitro using the blood perfused juxtamedullary nephron technique. This unique preparation provides direct accessibility to afferent and efferent arterioles of the rat kidney in a blood perfused setting. Importantly, this is accomplished while preserving the anatomical relationships between the tubules and vasculature and allowing direct study of renal microcirculatory regulation under well-controlled conditions. This technique is highly sophisticated and has already made major contributions to defining what is known about renal hemodynamic control and renal microvascular function. By applying this unique approach we will address three basic specific aims. Aim 1 will determine the effect of aging on myogenic and tubuloglomerular feedback mediated autoregulatory efficiency in male and female rats. Aim 2 will directly assess segmental renal microvascular responsiveness to the renal vasoconstrictors, endothelin and angiotensin II. Aim 3 will directly assess the renal microvascular responsiveness to endothelium-dependent and endothelium-independent renal vasodilators, acetylcholine and nitric oxide. The data obtained will provide an accurate view of the behavior of afferent and efferent arterioles in young and aged, male and female rats. They will also provide the first direct functional evidence of the efficiency of renal autoregulatory behavior as well as the fundamental responsiveness to critically important renal vasoconstrictors and vasodilators. Application of these approaches to the study of microvascular function in kidneys of aged animals promises to provide unique insight into the impact of aging on microvascular function and renal microcirculatory regulation.

该 NIA 试点研究补助金申请 (RO3) 的重点是直接检查衰老动物肾脏的肾微血管功能，目的是建立主要微血管功能的关键数据，并获得必要的初步数据，以准备更全面的 RO1 提案来年。目前，还没有研究直接检查老年动物的肾微血管功能，但肾功能下降通常与年龄相关的生理性心血管稳态下降有关。将使用血液灌注近髓肾单位技术在体外进行实验。这种独特的制剂可在血液灌注环境中直接进入大鼠肾脏的传入和传出小动脉。重要的是，这是在保留肾小管和脉管系统之间的解剖关系的同时实现的，并允许在良好控制的条件下直接研究肾脏微循环调节。这项技术非常复杂，已经为定义肾脏血流动力学控制和肾微血管功能的已知知识做出了重大贡献。通过应用这种独特的方法，我们将实现三个基本的具体目标。 目标 1 将确定衰老对雄性和雌性大鼠生肌和肾小球反馈介导的自动调节效率的影响。 目标 2 将直接评估肾血管收缩剂、内皮素和血管紧张素 II 的节段肾微血管反应性。目标 3 将直接评估肾微血管对内皮依赖性和内皮非依赖性肾血管扩张剂、乙酰胆碱和一氧化氮的反应性。 获得的数据将提供年轻和老年、雄性和雌性大鼠传入和传出小动脉行为的准确视图。他们还将提供第一个直接的功能证据，证明肾脏自动调节行为的效率以及对至关重要的肾脏血管收缩剂和血管扩张剂的基本反应性。 将这些方法应用于老年动物肾脏微血管功能的研究有望为衰老对微血管功能和肾脏微循环调节的影响提供独特的见解。