MODEL OF THE RENAL MEDULLARY MICROCIRCULATORY FUNCTION

肾髓微循环功能模型

• 批准号: 6635091
• 负责人: AURELIE EDWARDS
• 金额: $ 11.45万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-15 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635091
• 关键词: electrolyte balance; hormone regulation /control mechanism; kidney circulation; mathematical model; model design /development; nitric oxide; osmotic pressure; oxygen tension; oxygen transport; renal ischemia /hypoxia; renal medulla; renal tubular transport; urea; water channel

The production of maximally concentrated urine is made possible by the renal countercurrent multiplication system, which generates and maintains a hypertonic inner medulla, comprised of cortico- medullary gradients of NaCl and urea. Many features of the multiplication system remain to be elucidated, in particular the role of the medullary microcirculation. By modulating blood flow, vasa recta (i.e., the blood vessels in the renal medulla) can have a major effect on sodium and water homeostasis as well as on the long-term control of arterial blood pressure; their role in hypertension and congestive heart failure is thus highly relevant. Changes in renal medullary hemodynamics are also directly involved in pressure natriuresis. The overall goal of this research is to develop a comprehensive mathematical model of the renal medullary microcirculatory function in order to predict the efficiency of countercurrent exchange of water, small solutes, and macromolecules by the vasa recta. The specific aims of this project are the following. 1. To investigate the specific role of water channels (AQP-1) and urea transporters in descending vasa recta, incorporating data obtained on wildtype mice, AQP-1 deficient mice and AQP-1 deficient mice in which the AQP-1 gene has been replaced by means of an adenovirus. 2. To determine the mechanisms that control interstitial albumin concentration. The effects of albumin concentration polarization at the vessel walls will be determined as a first step. 3. To model the transport of oxygen in the renal medulla and to examine the effects of changes in blood flow rate and tubular consumption on oxygen tension. Medullary hypoxia is a consequence of the need for countercurrent exchange; however, too little oxygen can cause medullary hypoxic injury. 4. To examine how secretion of the vasoactive hormone nitric oxide into the vascular exchanger affects medullary blood flow and interstitial osmolality, and to investigate the relationship between the reduced medullary hematocrit, medullary hypoxia and the effectiveness of NO in the medulla.

通过肾逆流增殖系统可以产生最大浓度的尿液，该系统产生并维持高渗的内髓质，由NaCl和尿素的皮质-髓质梯度组成。增殖系统的许多特征仍有待阐明，特别是髓质微循环的作用。通过调节血流，直血管（即，肾髓质中的血管）可对钠和水的体内平衡以及对动脉血压的长期控制具有主要影响;因此它们在高血压和充血性心力衰竭中的作用是高度相关的。肾髓质血流动力学的变化也直接参与压力性钠尿排泄。本研究的总体目标是开发一个全面的数学模型的肾髓质微循环功能，以预测水，小溶质和大分子的直小血管的逆流交换的效率。该项目的具体目标如下。1.为了研究水通道（AQP-1）和尿素转运蛋白在下行直血管中的特定作用，结合从野生型小鼠、AQP-1缺陷小鼠和AQP-1基因已被腺病毒取代的AQP-1缺陷小鼠中获得的数据。2.确定控制间质白蛋白浓度的机制。作为第一步，将确定血管壁处白蛋白浓度极化的影响。3.建立肾脏髓质中氧运输的模型，并检查血流速度和肾小管消耗变化对氧张力的影响。髓缺氧是需要逆流交换的结果;然而，太少的氧气可导致髓缺氧损伤。4.研究血管活性激素一氧化氮（NO）分泌到血管交换器中对髓质血流量和间质渗透压的影响，探讨髓质红细胞压积降低、髓质缺氧与NO在髓质中的作用之间的关系。