期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：35
页码：13068-13073
DOI：10.1073/pnas.0405179101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Normal variations in glomerular filtration induce proportional changes in proximal tubule Na+ reabsorption. This "glomerulotubular balance" derives from flow dependence of Na+ uptake across luminal cell membranes; however, the underlying physical mechanism is unknown. Our hypothesis is that flow-dependent reabsorption is an autoregulatory mechanism that is independent of neural and hormonal systems. It is signaled by the hydrodynamic torque (bending moment) on epithelial microvilli. Such signals need to be transmitted to the terminal web to modulate Na+-H+-exchange activity. To investigate this hypothesis, we examined Na+ transport and tubular diameter in response to different flow rates during the microperfusion of isolated S2 proximal tubules from mouse kidneys. The data were analyzed by using a mathematical model to estimate the microvillous torque as function of flow. In this model, increases in luminal diameter have the effect of blunting the impact of flow velocity on microvillous shear stress and, thus, microvillous torque. We found that variations in microvillous torque produce nearly identical fractional changes in Na+ reabsorption. Furthermore, the flow-dependent Na+ transport is increased by increasing luminal fluid viscosity, diminished in Na+-H+ exchanger isoform 3 knockout mice, and abolished by nontoxic disruption of the actin cytoskeleton. These data support our hypothesis that the "brush-border" microvilli serve a mechanosensory function in which fluid dynamic torque is transmitted to the actin cytoskeleton and modulates Na+ absorption in kidney proximal tubules.
关键词：glomerulotubular balance ; flow-dependent transport ; Na+-H+ exchange
