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incorporating data obtained on wildtype mice, AQP-1 deficient mice and AQP-1 deficient mice in which the AQP-1 gene has been replaced by means of an adenovirus. 2.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.

肾脏逆流倍增系统可以产生最大程度浓缩的尿液，该系统产生并维持高渗的内髓质，由氯化钠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，直肠血管（即肾髓质中的血管）可以对钠和水的稳态以及动脉血压的长期控制产生重大影响；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尿钠排泄。本研究的总体目标是开发肾髓质微循环功能的综合数学模型，以预测直肠水、小溶质和大分子逆流交换的效率。该项目的具体目标如下。 1. 结合野生型小鼠、AQP-1 缺陷型小鼠和 AQP-1 基因已被去除的 AQP-1 缺陷型小鼠获得的数据，研究水通道 (AQP-1) 和尿素转运蛋白在直肠下行血管中的具体作用。被腺病毒替代。 2. 确定控制间质白蛋白浓度的机制。第一步将确定白蛋白浓差极化对血管壁的影响。 3. 模拟肾髓质中的氧输送并检查血流量和肾小管消耗的变化对氧张力的影响。髓质缺氧是逆流交换需要的结果；然而，氧气太少会导致髓质缺氧损伤。 4. 探讨血管活性激素一氧化氮分泌到血管交换器中对髓质血流量和间质渗透压的影响，并探讨髓质红细胞压积降低、髓质缺氧与髓质NO有效性之间的关系。