Modeling Solute Transport and Urine Concentrating Mechanism in the Rat Kidney

描述（由申请人提供）：模拟大鼠肾脏中的溶质转运和尿浓缩机制本提案的目标是使用数学建模来研究肾脏转运和动力学方面，最终目标是更好地理解哺乳动物尿浓缩机制和溶质循环。 将在以下研究中使用肾小管和微血管的数学模型，以及用于求解微分方程的显式分析和数值方法：（I）将开发大鼠肾脏中肾髓质的尿液浓缩机制的模型，该模型代表肾小管和血管的相对位置，并用于检验假设：大鼠肾内髓质的尿液浓缩机制是由肾小管内的溶质混合引起的，根据肾小管和血管之间特殊的三维关系，该机制可能由四个逆流系统组成。(II)内髓三维结构的一个特殊方面将被考虑：由集合管、升直血管和升细肢界定的间质结节空间。将使用隔室模型来检验这些微区可能是特定溶质的靶向递送和相互作用的必要混合节点的假设。(III)将开发尿液浓缩机制的动态模型，并用于跟踪溶质（特别是尿素）循环，研究溶质的停留时间，并研究尿素负荷的瞬态效应。最终目标是更好地了解尿素在肾髓质的再循环，以及在生理和病理生理条件下，髓质三维结构和逆流肾小管变性在尿素管理中的作用。(IV)本实验采用大鼠外髓内条切片模型，结合升支粗细胞上皮转运过程的详细图示，研究升支粗细胞的能量效率和钠转运。 公共卫生相关性：模拟大鼠肾脏溶质转运和尿液浓缩机制的意义。该提议旨在提供对肾脏可以产生比血浆更浓缩的尿液的手段的更完整和定量的理解（即，其每单位体积含有比血浆更多的溶质）。这一基础研究与公共卫生有关，因为已知肾脏尿液浓缩能力的异常会引起、促成、成为许多重要紊乱和疾病的后果或沿着发生，这些紊乱和疾病包括异常的身体水和盐保留或损失。

DESCRIPTION (provided by applicant): Modeling Solute Transport and Urine Concentrating Mechanism in the Rat Kidney The goal of this proposal is to use mathematical modeling to investigate aspects of the renal trans- port and dynamics, with an ultimate goal of gaining a better understanding of the mammalian urine concentrating mechanism and solute cycling. Mathematical models of renal tubules and microvessels, coupled with explicit analysis and numerical methods for solving dierential equations, will be used in the following studies: (I) A model of the urine concentrating mechanism of the renal medulla in the rat kidney that represents the relative positions of the tubules and vessels will be developed and used to test the hypothesis: the urine concentrating mechanism of the renal inner medulla of the rat kidney arises from solute mixing in the interstitium, and that mechanism may be comprised of four countercurrent systems, based on the specic 3-dimensional relationships among tubules and vessels. (II) A specic aspect of the 3-dimensional organization in the inner medulla will be considered: interstitial nodal spaces that are bordered by collecting ducts, ascending vasa recta, and ascending thin limbs. A compartment model will be used to test the hypothesis that these microdomains may be essential mixing nodes for targeted delivery and interaction of specic solutes. (III) A dynamic model of the urine concentrating mechanism will be developed and used to track solute (urea, in particular) cycling, to study residence times of solutes, and to study the transient eects of urea loads. The ultimate goal is to gain a better understanding of urea recycling in the renal medulla, and the role of medullary 3-dimensional structure and countercurrent tubular conguration in urea management under physiologic and pathophysiologic conditions. (IV) A slice model of the inner stripe of the rat outer medulla, together with a detailed representation of the epithelial transport processes of the thick ascending limb cell, will be used to study the energy eciency and sodium transport of the thick ascending limbs. PUBLIC HEALTH RELEVANCE: Modeling Solute Transport and Urine Concentrating Mechanism of the Rat Kidney Significance. This proposal aims to provide a more complete and quantitative understanding of the means by which the kidney can produce urine that is more concentrated than blood plasma (i.e., that contains more solute per unit volume than does blood plasma). This basic research is relevant to public health, because abnormalities of the kidney's urine concentrating capability are known to cause, contribute to, be a consequence of, or occur along with, a number of important disorders and diseases, including abnormal body water and salt retention or loss.