RENAL MICROVASCULAR FUNCTION IN AGED RATS

该NIA试点研究资助申请（RO3）的重点是直接检查老年动物肾脏中的肾脏微血管功能，以建立有关主要微血管功能的关键数据，并获得必要的初步数据，以便在来年准备更全面的RO1提案。目前，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。实验将在体外使用血液灌注延髓肾单位技术进行。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血管系统之间的解剖关系的同时完成的，并允许在良好控制的条件下直接研究肾微循环调节。这项技术是高度复杂的，并已作出重大贡献，以确定什么是已知的肾血流动力学控制和肾微血管功能。通过采用这种独特的方法，我们将解决三个基本的具体目标。 目的1：研究增龄对雄性和雌性大鼠肌源性和管球反馈介导的自我调节效率的影响。 目的2将直接评估节段性肾微血管对肾血管收缩剂内皮素和血管紧张素II的反应性。目的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舒张剂乙酰胆碱和一氧化氮的反应性。 所获得的数据将提供年轻和老年、雄性和雌性大鼠的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的效率，肾脏的自我调节行为，以及基本的反应，至关重要的肾血管收缩剂和血管扩张剂。 应用这些方法研究老年动物肾脏的微血管功能，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。

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.