MODEL OF THE RENAL MEDULLARY MICROCIRCULATORY FUNCTION

肾脏逆流倍增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，由皮质-髓质梯度的氯化钠和尿素组成。增殖系统的许多特征仍有待阐明，特别是骨髓微循环的作用。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对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改变也直接与压力性钠尿有关。这项研究的总体目标是建立一个全面的肾脏髓质微循环功能的数学模型，以预测直肠血管逆流交换水、小溶质和大分子的效率。该项目的具体目标如下。1.结合野生型小鼠、AQP-1基因缺陷小鼠和AQP-1基因缺陷小鼠的研究结果，探讨水通道(AQP-1)和尿素转运体在直肠血管下行中的特殊作用。2.确定控制间质白蛋白浓度的机制。作为第一步，将确定血管壁上白蛋白浓度极化的影响。3.建立肾髓质氧转运模型，观察血流速度和肾小管消耗量的变化对肾髓质氧分压的影响。髓内缺氧是需要逆流交换的结果；然而，氧气过少会导致髓内缺氧损伤。4.观察血管活性激素一氧化氮分泌到血管交换器对髓内血流量和间质渗透压的影响，探讨髓内红细胞压积降低、髓内缺氧与髓内NO作用的关系。

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data obtained on wildtype mice, AQP-1 deficient mice and AQP-1 deficient mice in which the AQP-1 gene has been replaced by means of an adenovirus. 2.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