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Volker Vallon - One of the best experts on this subject based on the ideXlab platform.
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ecto 5 nucleotidase cd73 dependent and independent generation of adenosine participates in the mediation of tubuloglomerular feedback in vivo
American Journal of Physiology-renal Physiology, 2006Co-Authors: Dan Yang Huang, Volker Vallon, Herbert Zimmermann, Patricia Koszalka, Jurgen Schrader, Hartmut OsswaldAbstract:Tubuloglomerular feedback (TGF) describes a sequence of events linking salt concentrations in Tubular Fluid at the macula densa to the vascular tone of the afferent arteriole and thus to the glomer...
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tubuloglomerular feedback and the control of glomerular filtration rate
Physiology, 2003Co-Authors: Volker VallonAbstract:In every nephron the glomerular filtration rate is adapted to changes in the salt concentration of early distal Tubular Fluid through the mechanism of tubuloglomerular feedback. Recent studies indicate that adenosine and possibly ATP mediate this mechanism and demonstrate its role in glomerular hemodynamic alterations in the early diabetic kidney.
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tubuloglomerular feedback in the kidney insights from gene targeted mice
Pflügers Archiv: European Journal of Physiology, 2003Co-Authors: Volker VallonAbstract:The term tubuloglomerular feedback (TGF) refers to a series of events whereby changes in the concentration of Na+, Cl– and K+ in the distal Tubular Fluid are sensed by the macula densa and elicit reciprocal changes in nephron filtration rate (SNGFR). Although micropuncture experiments in the rat and studies in the isolated perfused rabbit juxtaglomerular apparatus (JGA) have yielded significant insights into TGF, many aspects, including the signal transduction and modulation in JGA and the role of TGF in physiology and pathophysiology, are still incompletely understood. This is due in part to the lack of selective drugs for inhibiting or activating a given molecule of interest and to the limited accessibility of target structures or molecules. Adaptation of single-nephron methods to gene-targeted mice is a promising approach for gaining further insights into TGF. The gist of the presently available studies in gene-targeted mice that are reviewed here support the concept that (i) adenosine mediates TGF by activation of adenosine A1 receptors; (ii) that this response is modulated inversely by nitric oxide synthase 1 activity in macula densa and activation of angiotensin II AT1A receptors; and (iii) that the TGF-dependent reduction in SNGFR prevents excessive renal Fluid and salt loss during primary inhibition of reabsorption upstream from the macula densa.
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role of kcne1 dependent k fluxes in mouse proximal tubule
Journal of The American Society of Nephrology, 2001Co-Authors: Volker Vallon, Florian Grahammer, Kerstin Richter, Markus Bleich, Florian Lang, Jacques Barhanin, Harald Volkl, Richard WarthAbstract:Abstract . The electrochemical gradient for K + across the luminal membrane of the proximal tubule favors K + fluxes to the lumen. Here it was demonstrated by immunohistochemistry that KCNE1 and KCNQ1, which form together the slowly activated component of the delayed rectifying K + current in the heart, also colocalize in the luminal membrane of proximal tubule in mouse kidney. Micropuncture experiments revealed a reduced K + concentration in late proximal and early distal Tubular Fluid as well as a reduced K + delivery to these sites in KCNE1 knockout (-/-), compared with wild-type (+/+) mice. These observations would be consistent with KCNE1-dependent K + fluxes to the lumen in proximal tubule. Electrophysiological studies in isolated perfused proximal tubules indicated that this K + flux is essential to counteract membrane depolarization due to electrogenic Na + -coupled transport of glucose or amino acids. Clearance studies revealed an enhanced fractional urinary excretion of Fluid, Na + , Cl - , and glucose in KCNE1 -/- compared with KCNE1 +/+ mice that may relate to an attenuated transport in proximal tubule and contribute to volume depletion in these mice, as indicated by higher hematocrit values.
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luminal hypotonicity in proximal tubules of aquaporin 1 knockout mice
American Journal of Physiology-renal Physiology, 2000Co-Authors: Volker Vallon, A S Verkman, Jurgen SchnermannAbstract:To examine the role of aquaporin-1 (AQP1) in near-isosmolar Fluid reabsorption in the proximal tubule, we compared osmolalities in micropuncture samples of late proximal Tubular Fluid and plasma in...
Anita T. Layton - One of the best experts on this subject based on the ideXlab platform.
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Profiles of Tubular Fluid solute concentrations (A–D), osmolality (E), and pH (F).
2019Co-Authors: Anita T. Layton, Harold E LaytonAbstract:Solid black lines, superficial nephron. Solid line, luminal Fluid solute concentrations, pH, and osmolality. Dashed lines, interstitial values. PT, proximal tubule; DL, descending limb; LDL/LAL, thin descending/ascending limb; TAL, thick ascending limb; DCT, distal convoluted tubule; CNT, connecting duct; CD, collecting duct.
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Modeling the effects of positive and negative feedback in kidney blood flow control.
Bellman Prize in Mathematical Biosciences, 2016Co-Authors: Anita T. LaytonAbstract:Abstract Blood flow in the mammalian kidney is tightly autoregulated. One of the important autoregulation mechanisms is the myogenic response, which is activated by perturbations in blood pressure along the afferent arteriole. Another is the tubuloglomerular feedback, which is a negative feedback that responds to variations in Tubular Fluid [Cl − ] at the macula densa. 1 When initiated, both the myogenic response and the tubuloglomerular feedback adjust the afferent arteriole muscle tone. A third mechanism is the connecting tubule glomerular feedback, which is a positive feedback mechanism located at the connecting tubule, downstream of the macula densa. The connecting tubule glomerular feedback is much less well studied. The goal of this study is to investigate the interactions among these feedback mechanisms and to better understand the effects of their interactions. To that end, we have developed a mathematical model of solute transport and blood flow control in the rat kidney. The model represents the myogenic response, tubuloglomerular feedback, and connecting tubule glomerular feedback. By conducting a bifurcation analysis, we studied the stability of the system under a range of physiologically-relevant parameters. The bifurcation results were confirmed by means of a comparison with numerical simulations. Additionally, we conducted numerical simulations to test the hypothesis that the interactions between the tubuloglomerular feedback and the connecting tubule glomerular feedback may give rise to a yet-to-be-explained low-frequency oscillation that has been observed in experimental records.
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Tubular Fluid flow and distal NaCl delivery mediated by tubuloglomerular feedback in the rat kidney
Journal of Mathematical Biology, 2014Co-Authors: Hwayeon Ryu, Anita T. LaytonAbstract:The glomerular filtration rate in the kidney is controlled, in part, by the tubuloglomerular feedback (TGF) system, which is a negative feedback loop that mediates oscillations in Tubular Fluid flow and in Fluid NaCl concentration of the loop of Henle. In this study, we developed a mathematical model of the TGF system that represents NaCl transport along a short loop of Henle with compliant walls. The proximal tubule and the outer-stripe segment of the descending limb are assumed to be highly water permeable; the thick ascending limb (TAL) is assumed to be water impermeable and have active NaCl transport. A bifurcation analysis of the TGF model equations was performed by computing parameter boundaries, as functions of TGF gain and delay, that separate differing model behaviors. The analysis revealed a complex parameter region that allows a variety of qualitatively different model equations: a regime having one stable, time-independent steady-state solution and regimes having stable oscillatory solutions of different frequencies. A comparison with a previous model, which represents only the TAL explicitly and other segments using phenomenological relations, indicates that explicit representation of the proximal tubule and descending limb of the loop of Henle lowers the stability of the TGF system. Model simulations also suggest that the onset of limit-cycle oscillations results in increases in the time-averaged distal NaCl delivery, whereas distal Fluid delivery is not much affected.
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signal transduction in a compliant short loop of henle
International Journal for Numerical Methods in Biomedical Engineering, 2012Co-Authors: Anita T. Layton, Philip Pham, Hwayeon RyuAbstract:To study the transformation of fluctuations in filtration rate into Tubular Fluid chloride concentration oscillations alongside the macula densa, we have developed a mathematical model for tubuloglomerular feedback (TGF) signal transduction along the pars recta, the descending limb, and the thick ascending limb of a short-looped nephron. The model tubules are assumed to have compliant walls and thus a Tubular radius that depends on the transmural pressure difference. Previously it has been predicted that TGF transduction by the thick ascending limb (TAL) is a generator of nonlinearities: if a sinusoidal oscillation is added to a constant TAL flow rate, then the time required for a Fluid element to traverse the TAL is oscillatory in time but nonsinusoidal. The results from the new model simulations presented here predict that TGF transduction by the loop of Henle is also, in the same sense, a generator of nonlinearities. Thus this model predicts that oscillations in Tubular Fluid alongside the macula densa will be nonsinusoidal and will exhibit harmonics of sinusoidal perturbations of pars recta flow. Model results also indicate that the loop acts as a low-pass filter in the transduction of the TGF signal.
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feedback mediated dynamics in a model of coupled nephrons with compliant thick ascending limbs
Bellman Prize in Mathematical Biosciences, 2011Co-Authors: Anita T. Layton, Matthew Bowen, Amy M Wen, Harold E LaytonAbstract:The tubuloglomerular feedback (TGF) system in the kidney, a key regulator of glomerular filtration rate, has been shown in physiologic experiments in rats to mediate oscillations in thick ascending limb (TAL) Tubular Fluid pressure, flow, and NaCl concentration. In spontaneously hypertensive rats, TGF-mediated flow oscillations may be highly irregular. We conducted a bifurcation analysis of a mathematical model of nephrons that are coupled through their TGF systems; the TALs of these nephrons are assumed to have compliant Tubular walls. A characteristic equation was derived for a model of two coupled nephrons. Analysis of that characteristic equation has revealed a number of parameter regions having the potential for differing stable dynamic states. Numerical solutions of the full equations for two model nephrons exhibit a variety of behaviors in these regions. Also, model results suggest that the stability of the TGF system is reduced by the compliance of TAL walls and by internephron coupling; as a result, the likelihood of the emergence of sustained oscillations in Tubular Fluid pressure and flow is increased. Based on information provided by the characteristic equation, we identified parameters with which the model predicts irregular Tubular flow oscillations that exhibit a degree of complexity that may help explain the emergence of irregular oscillations in spontaneously hypertensive rats.
Joost P. Schanstra - One of the best experts on this subject based on the ideXlab platform.
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Renal Tubular Fluid shear stress facilitates monocyte activation toward inflammatory macrophages
American Journal of Physiology-renal Physiology, 2012Co-Authors: Mathieu Miravete, Romain Dissard, Julien Gonzalez, Bernard Pipy, Christiane Pecher, Jean Loup Bascands, Cécile Caubet, Julie Klein, Muriel Mercier-bonin, Joost P. SchanstraAbstract:Modified urinary Fluid shear stress (FSS) induced by variations of urinary Fluid flow and composition is observed in early phases of most kidney diseases. Recently, we reported that renal Tubular F...
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Renal Tubular Fluid shear stress promotes endothelial cell activation.
Biochemical and Biophysical Research Communications, 2011Co-Authors: Mathieu Miravete, Julien Gonzalez, Christiane Pecher, Jean Loup Bascands, Joost P. Schanstra, Julie Klein, Muriel Mercier-bonin, Aurèle Besse-patin, Bénédicte Buffin-meyerAbstract:Modified urinary Fluid shear stress (FSS) induced by variations of urinary Fluid flow and composition is observed in early phases of most kidney diseases. In this study, we hypothesized that changes in urinary FSS represent a Tubular aggression that contributes to the development of inflammation, a key event in progression of nephropathies. Human renal Tubular cells (HK-2) were exposed to FSS for 30 min at 0.01 Pa. Treatment of human endothelial cells (HMEC-1) with the resulting conditioned medium (FSS-CM) increased C-C chemokine ligand 2 (CCL2) and tumor necrosis factor (TNF)-α protein secretion, increased endothelial vascular adhesion molecule-1 (VCAM-1) mRNA expression and stimulated adhesion of human (THP-1) monocytes to the endothelial monolayer. These effects were TNF-α dependent as they were abolished by neutralization of TNF-α. Interestingly, the origin of TNF-α was not epithelial, but resulted from autocrine endothelial production. However, in contrast to short term FSS, long term FSS (5h) induced the release of the key inflammatory proteins CCL2 and TNF-α directly from Tubular cells. In conclusion, these results suggest for the first time that urinary FSS can contribute to the inflammatory state involved in initiation/perpetuation of renal diseases.
Mathieu Miravete - One of the best experts on this subject based on the ideXlab platform.
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Renal Tubular Fluid shear stress facilitates monocyte activation toward inflammatory macrophages
American Journal of Physiology-renal Physiology, 2012Co-Authors: Mathieu Miravete, Romain Dissard, Julien Gonzalez, Bernard Pipy, Christiane Pecher, Jean Loup Bascands, Cécile Caubet, Julie Klein, Muriel Mercier-bonin, Joost P. SchanstraAbstract:Modified urinary Fluid shear stress (FSS) induced by variations of urinary Fluid flow and composition is observed in early phases of most kidney diseases. Recently, we reported that renal Tubular F...
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Renal Tubular Fluid shear stress promotes endothelial cell activation.
Biochemical and Biophysical Research Communications, 2011Co-Authors: Mathieu Miravete, Julien Gonzalez, Christiane Pecher, Jean Loup Bascands, Joost P. Schanstra, Julie Klein, Muriel Mercier-bonin, Aurèle Besse-patin, Bénédicte Buffin-meyerAbstract:Modified urinary Fluid shear stress (FSS) induced by variations of urinary Fluid flow and composition is observed in early phases of most kidney diseases. In this study, we hypothesized that changes in urinary FSS represent a Tubular aggression that contributes to the development of inflammation, a key event in progression of nephropathies. Human renal Tubular cells (HK-2) were exposed to FSS for 30 min at 0.01 Pa. Treatment of human endothelial cells (HMEC-1) with the resulting conditioned medium (FSS-CM) increased C-C chemokine ligand 2 (CCL2) and tumor necrosis factor (TNF)-α protein secretion, increased endothelial vascular adhesion molecule-1 (VCAM-1) mRNA expression and stimulated adhesion of human (THP-1) monocytes to the endothelial monolayer. These effects were TNF-α dependent as they were abolished by neutralization of TNF-α. Interestingly, the origin of TNF-α was not epithelial, but resulted from autocrine endothelial production. However, in contrast to short term FSS, long term FSS (5h) induced the release of the key inflammatory proteins CCL2 and TNF-α directly from Tubular cells. In conclusion, these results suggest for the first time that urinary FSS can contribute to the inflammatory state involved in initiation/perpetuation of renal diseases.
Hwayeon Ryu - One of the best experts on this subject based on the ideXlab platform.
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Tubular Fluid flow and distal NaCl delivery mediated by tubuloglomerular feedback in the rat kidney
Journal of Mathematical Biology, 2014Co-Authors: Hwayeon Ryu, Anita T. LaytonAbstract:The glomerular filtration rate in the kidney is controlled, in part, by the tubuloglomerular feedback (TGF) system, which is a negative feedback loop that mediates oscillations in Tubular Fluid flow and in Fluid NaCl concentration of the loop of Henle. In this study, we developed a mathematical model of the TGF system that represents NaCl transport along a short loop of Henle with compliant walls. The proximal tubule and the outer-stripe segment of the descending limb are assumed to be highly water permeable; the thick ascending limb (TAL) is assumed to be water impermeable and have active NaCl transport. A bifurcation analysis of the TGF model equations was performed by computing parameter boundaries, as functions of TGF gain and delay, that separate differing model behaviors. The analysis revealed a complex parameter region that allows a variety of qualitatively different model equations: a regime having one stable, time-independent steady-state solution and regimes having stable oscillatory solutions of different frequencies. A comparison with a previous model, which represents only the TAL explicitly and other segments using phenomenological relations, indicates that explicit representation of the proximal tubule and descending limb of the loop of Henle lowers the stability of the TGF system. Model simulations also suggest that the onset of limit-cycle oscillations results in increases in the time-averaged distal NaCl delivery, whereas distal Fluid delivery is not much affected.
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signal transduction in a compliant short loop of henle
International Journal for Numerical Methods in Biomedical Engineering, 2012Co-Authors: Anita T. Layton, Philip Pham, Hwayeon RyuAbstract:To study the transformation of fluctuations in filtration rate into Tubular Fluid chloride concentration oscillations alongside the macula densa, we have developed a mathematical model for tubuloglomerular feedback (TGF) signal transduction along the pars recta, the descending limb, and the thick ascending limb of a short-looped nephron. The model tubules are assumed to have compliant walls and thus a Tubular radius that depends on the transmural pressure difference. Previously it has been predicted that TGF transduction by the thick ascending limb (TAL) is a generator of nonlinearities: if a sinusoidal oscillation is added to a constant TAL flow rate, then the time required for a Fluid element to traverse the TAL is oscillatory in time but nonsinusoidal. The results from the new model simulations presented here predict that TGF transduction by the loop of Henle is also, in the same sense, a generator of nonlinearities. Thus this model predicts that oscillations in Tubular Fluid alongside the macula densa will be nonsinusoidal and will exhibit harmonics of sinusoidal perturbations of pars recta flow. Model results also indicate that the loop acts as a low-pass filter in the transduction of the TGF signal.
