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Thomas L Pallone - One of the best experts on this subject based on the ideXlab platform.
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interstitial water and solute recovery by inner Medullary vasa recta
American Journal of Physiology-renal Physiology, 2000Co-Authors: Aurélie Edwards, Mark J Delong, Thomas L PalloneAbstract:A recent model of volume and solute microvascular exchange in the renal medulla was extended by simulating the deposition of NaCl, urea, and water into the Medullary Interstitium from the loops of ...
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Molecular sieving of small solutes by outer Medullary descending vasa recta.
The American journal of physiology, 1997Co-Authors: Thomas L Pallone, M R TurnerAbstract:Molecular sieving of small solutes by outer Medullary descending vasa recta (OMDVR). Descending vasa recta (DVR) plasma equilibrates with the Medullary Interstitium by volume efflux (Jv), as well as by influx of solutes. Jv is driven by transmural osmotic pressure gradients due to small hydrophilic solutes (delta pi s), NaCl and urea. DVR endothelium probably contains a "water-only" pathway most likely mediated by the aquaporin-1 (AQP1) water channel. We measured the ability of microperfused OMDVR to concentrate lumenal 22Na and [3H]raffinose when Jv was driven by transmural NaCl gradients. Collectate-to-perfusate ratios of 2 x 10(6) M(r) fluorescein isothiocyanate-labeled dextran volume marker (RDx), 22Na (RNa), and [3H]raffinose (Rraf) were measured in the absence and presence of Jv. During volume efflux (Jv > 0), RDx was 1.37 +/- 0.31. RNa increased from 0.64 +/- 0.03 when Jv = 0 to 0.82 +/- 0.05 when Jv > 0 and Rraf increased from 0.83 +/- 0.03 to 1.13 +/- 0.05: Mathematical simulations predict RNa and Rraf most accurately when the OMDVR reflection coefficient to the tracers is assigned a value near unity. This indicates that the OMDVR wall contains a pathway for osmotic volume flux that excludes small hydrophilic solutes, a behavior consistent with that of aquaporins.
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molecular sieving of small solutes by outer Medullary descending vasa recta
American Journal of Physiology-renal Physiology, 1997Co-Authors: Thomas L Pallone, M R TurnerAbstract:Molecular sieving of small solutes by outer Medullary descending vasa recta (OMDVR). Descending vasa recta (DVR) plasma equilibrates with the Medullary Interstitium by volume efflux (Jv), as well as by influx of solutes. Jv is driven by transmural osmotic pressure gradients due to small hydrophilic solutes (delta pi s), NaCl and urea. DVR endothelium probably contains a "water-only" pathway most likely mediated by the aquaporin-1 (AQP1) water channel. We measured the ability of microperfused OMDVR to concentrate lumenal 22Na and [3H]raffinose when Jv was driven by transmural NaCl gradients. Collectate-to-perfusate ratios of 2 x 10(6) M(r) fluorescein isothiocyanate-labeled dextran volume marker (RDx), 22Na (RNa), and [3H]raffinose (Rraf) were measured in the absence and presence of Jv. During volume efflux (Jv > 0), RDx was 1.37 +/- 0.31. RNa increased from 0.64 +/- 0.03 when Jv = 0 to 0.82 +/- 0.05 when Jv > 0 and Rraf increased from 0.83 +/- 0.03 to 1.13 +/- 0.05: Mathematical simulations predict RNa an...
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facilitated transport in vasa recta theoretical effects on solute exchange in the Medullary microcirculation
American Journal of Physiology-renal Physiology, 1997Co-Authors: Aurélie Edwards, Thomas L PalloneAbstract:A new theoretical model describing the exchange of water and solutes between the renal Medullary Interstitium and the microcirculation was developed to account for the presence of water channels and urea transporters, both of which were recently identified in the descending vasa recta (DVR) of the renal medulla. Small solutes, which are excluded from the water channels, are freely exchanged through a parallel pathway shared with water. The transcapillary concentration gradients of sodium and urea across the water channels induce water efflux from DVR, whereas classic Starling forces across the shared pathway favor volume uptake by DVR. Because small solute concentration gradients are large in the inner medulla, the model predicts net water removal from DVR, in agreement with experimental observations. The descending and ascending vasa recta (AVR) function as a countercurrent exchanger, the efficiency of which is inversely related to the net amount of solute taken up by the Medullary microcirculation. Our results indicate that net solute removal from the medulla is governed by convective uptake into AVR and thus depends predominantly on the parameters affecting AVR transcapillary volume flux. The simulations also suggest that the urea transporter significantly enhances the exchange of both sodium and urea and might serve to abrogate a reduction in exchanger efficiency imparted by water channels.
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Extravascular protein in the renal medulla: analysis by two methods
American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 1994Co-Authors: Thomas L PalloneAbstract:Two methods have been used to test for the presence of extravascular protein in the Interstitium of the renal inner medulla. First, ascending vasa recta (AVR) segments were perfused with buffer containing 5 g/dl of albumin. The hydraulic pressure in the perfused vessel was varied to control transmembrane volume flux (Jv) to the Interstitium. Interpolation to the point of zero Jv was employed to estimate interstitial Starling forces in the hydropenic rat papilla. Analysis of those experiments predicts that interstitial protein concentration (Ci) is high. When AVR segments are filled with oil, the oil column spontaneously breaks up as fluid is secreted into the lumen from the papillary Interstitium. To obtain a lower limit on Ci, isolated AVR segments (IAS) filled with oil were sampled to measure protein concentration in the secreted fluid. In hydropenic rats, protein concentration was 3.4 +/- 0.5 and 5.2 +/- 0.2 g/dl in IAS and adjacent free-flowing AVR, respectively (P < 0.01). In rats subjected to furosemide and saline diuresis, the values were nearly identical, 4.7 +/- 0.2 and 5.2 +/- 0.2 g/dl, respectively. These separate experimental approaches corroborate a high concentration of protein in the renal inner Medullary Interstitium.
Moo H Kwon - One of the best experts on this subject based on the ideXlab platform.
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interstitial tonicity controls tonebp expression in the renal medulla
Kidney International, 2009Co-Authors: Mee Rie Sheen, Un Sil Jeon, Juy Jung, Sooh Park, Moo H KwonAbstract:Cells in the hyperosmotic kidney medulla, express a transcriptional activator termed tonicity responsive enhancer binding protein (TonEBP). Genes targeted by TonEBP protect kidney cells from the deleterious effects of hyperosmolality by inducing the expression of organic osmolytes and molecular chaperones, and other genes that mediate urine concentration such as aquaporin-2 and urea transporters. We tested here the effect of hypertonicity and hyperosmotic salt in the renal Medullary Interstitium on the expression TonEBP. When massive water diuresis was induced in rats the Medullary sodium concentrations did not change, neither did TonEBP expression. In these animals the Medullary tonicity was unchanged despite the production of dilute urine. On the other hand, treatment with the loop diurectic furosemide resulted in a dose-dependent decrease in the Medullary sodium concentration causing a reduction in interstitial tonicity. Here, TonEBP expression was blunted in the outer and inner medulla which was due, in part, to decreased mRNA abundance. As expected, the expression of TonEBP target genes in the renal medulla also decreased in response to furosemide. Hence TonEBP expression in the renal medulla is stimulated by interstitial hypertonicity.
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downregulation of renal sodium transporters and tonicity responsive enhancer binding protein by long term treatment with cyclosporin a
Journal of The American Society of Nephrology, 2007Co-Authors: Mee Rie Sheen, Un Sil Jeon, Chul Woo Yang, Moo H KwonAbstract:Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator that is regulated by ambient tonicity. TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration. It was reported recently that long-term CsA treatment was associated with decreased renal expression of TonEBP target genes, including aquaporin-2, urea transporter, and aldose reductase. This study tested the hypothesis that long-term CsA treatment reduces the salinity/ tonicity of the renal Medullary Interstitium as a result of inhibition of active sodium transporters, leading to downregulation of TonEBP. CsA treatment for 7 d did not affect TonEBP or renal function. Whereas expression of sodium transporters was altered, the Medullary tonicity seemed unchanged. Conversely, 28 d of CsA treatment led to downregulation of TonEBP and overt nephrotoxicity. The downregulation of TonEBP involved reduced expression, cytoplasmic shift, and reduced transcription of its target genes. This was associated with reduced expression of active sodium transporters—sodium/potassium/ chloride transporter type 2 (NKCC2), sodium/chloride transporter, and Na,K-ATPase—along with increased sodium excretion and reduced urinary concentration. Infusion of vasopressin restored the expression of NKCC2 in the outer medulla as well as the expression and the activity of TonEBP. It is concluded that the downregulation of TonEBP in the setting of long-term CsA administration is secondary to the reduced tonicity of the renal Medullary Interstitium.
Aurélie Edwards - One of the best experts on this subject based on the ideXlab platform.
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Transport of plasma proteins across vasa recta in the renal medulla.
American journal of physiology. Renal physiology, 2001Co-Authors: Wensheng Zhang, Aurélie EdwardsAbstract:In this study, we have extended a mathematical model of microvascular exchange in the renal medulla to elucidate the mechanisms by which plasma proteins are transported between vasa recta and the Interstitium. In contrast with other work, a distinction was made between the paracellular pathway and the transcellular route (i.e., water channels) in descending vasa recta (DVR). Our model first indicates that concentration polarization on the interstitial side of vasa recta has a negligible effect on Medullary function. Our results also suggest that, whereas proteins are cleared from the Interstitium by convection, both diffusion and convection play a role in carrying proteins to the Interstitium. In those regions where transcapillary oncotic pressure gradients favor volume influx through the paracellular pathway in DVR, diffusion is the only means by which proteins can penetrate the Interstitium. Whether the source of interstitial protein is DVR or ascending vasa recta depends on Medullary depth, vasa recta permeability to proteins, and vasa recta reflection coefficients to small solutes and proteins. Finally, our model predicts significant axial protein gradients in the renal Medullary Interstitium.
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interstitial water and solute recovery by inner Medullary vasa recta
American Journal of Physiology-renal Physiology, 2000Co-Authors: Aurélie Edwards, Mark J Delong, Thomas L PalloneAbstract:A recent model of volume and solute microvascular exchange in the renal medulla was extended by simulating the deposition of NaCl, urea, and water into the Medullary Interstitium from the loops of ...
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facilitated transport in vasa recta theoretical effects on solute exchange in the Medullary microcirculation
American Journal of Physiology-renal Physiology, 1997Co-Authors: Aurélie Edwards, Thomas L PalloneAbstract:A new theoretical model describing the exchange of water and solutes between the renal Medullary Interstitium and the microcirculation was developed to account for the presence of water channels and urea transporters, both of which were recently identified in the descending vasa recta (DVR) of the renal medulla. Small solutes, which are excluded from the water channels, are freely exchanged through a parallel pathway shared with water. The transcapillary concentration gradients of sodium and urea across the water channels induce water efflux from DVR, whereas classic Starling forces across the shared pathway favor volume uptake by DVR. Because small solute concentration gradients are large in the inner medulla, the model predicts net water removal from DVR, in agreement with experimental observations. The descending and ascending vasa recta (AVR) function as a countercurrent exchanger, the efficiency of which is inversely related to the net amount of solute taken up by the Medullary microcirculation. Our results indicate that net solute removal from the medulla is governed by convective uptake into AVR and thus depends predominantly on the parameters affecting AVR transcapillary volume flux. The simulations also suggest that the urea transporter significantly enhances the exchange of both sodium and urea and might serve to abrogate a reduction in exchanger efficiency imparted by water channels.
Mee Rie Sheen - One of the best experts on this subject based on the ideXlab platform.
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interstitial tonicity controls tonebp expression in the renal medulla
Kidney International, 2009Co-Authors: Mee Rie Sheen, Un Sil Jeon, Juy Jung, Sooh Park, Moo H KwonAbstract:Cells in the hyperosmotic kidney medulla, express a transcriptional activator termed tonicity responsive enhancer binding protein (TonEBP). Genes targeted by TonEBP protect kidney cells from the deleterious effects of hyperosmolality by inducing the expression of organic osmolytes and molecular chaperones, and other genes that mediate urine concentration such as aquaporin-2 and urea transporters. We tested here the effect of hypertonicity and hyperosmotic salt in the renal Medullary Interstitium on the expression TonEBP. When massive water diuresis was induced in rats the Medullary sodium concentrations did not change, neither did TonEBP expression. In these animals the Medullary tonicity was unchanged despite the production of dilute urine. On the other hand, treatment with the loop diurectic furosemide resulted in a dose-dependent decrease in the Medullary sodium concentration causing a reduction in interstitial tonicity. Here, TonEBP expression was blunted in the outer and inner medulla which was due, in part, to decreased mRNA abundance. As expected, the expression of TonEBP target genes in the renal medulla also decreased in response to furosemide. Hence TonEBP expression in the renal medulla is stimulated by interstitial hypertonicity.
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downregulation of renal sodium transporters and tonicity responsive enhancer binding protein by long term treatment with cyclosporin a
Journal of The American Society of Nephrology, 2007Co-Authors: Mee Rie Sheen, Un Sil Jeon, Chul Woo Yang, Moo H KwonAbstract:Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator that is regulated by ambient tonicity. TonEBP protects the renal medulla from the deleterious effects of hyperosmolality and regulates the urinary concentration by stimulating aquaporin-2 and urea transporters. The therapeutic use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by reduced GFR, fibrosis, and tubular defects, including reduced urinary concentration. It was reported recently that long-term CsA treatment was associated with decreased renal expression of TonEBP target genes, including aquaporin-2, urea transporter, and aldose reductase. This study tested the hypothesis that long-term CsA treatment reduces the salinity/ tonicity of the renal Medullary Interstitium as a result of inhibition of active sodium transporters, leading to downregulation of TonEBP. CsA treatment for 7 d did not affect TonEBP or renal function. Whereas expression of sodium transporters was altered, the Medullary tonicity seemed unchanged. Conversely, 28 d of CsA treatment led to downregulation of TonEBP and overt nephrotoxicity. The downregulation of TonEBP involved reduced expression, cytoplasmic shift, and reduced transcription of its target genes. This was associated with reduced expression of active sodium transporters—sodium/potassium/ chloride transporter type 2 (NKCC2), sodium/chloride transporter, and Na,K-ATPase—along with increased sodium excretion and reduced urinary concentration. Infusion of vasopressin restored the expression of NKCC2 in the outer medulla as well as the expression and the activity of TonEBP. It is concluded that the downregulation of TonEBP in the setting of long-term CsA administration is secondary to the reduced tonicity of the renal Medullary Interstitium.
Soline Bourgeois - One of the best experts on this subject based on the ideXlab platform.
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Two Rhesus protein ammonia transporters team up to eliminate ammonium into urine
American journal of physiology. Renal physiology, 2014Co-Authors: Carsten A. Wagner, Soline BourgeoisAbstract:renal ammoniagenesis serves the de novo synthesis of bicarbonate consumed by metabolism and the excretion of acid. Ammonium is eventually excreted into urine after accumulation in the Medullary Interstitium. The process of ammonium excretion was long thought to be a mostly passive process mediated
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More actors in ammonia absorption by the thick ascending limb.
American journal of physiology. Renal physiology, 2011Co-Authors: Pascal Houillier, Soline BourgeoisAbstract:This review will briefly summarize current knowledge on the basolateral ammonia transport mechanisms in the thick ascending limb (TAL) of the loop of Henle. This segment transports ammonia against a concentration gradient and is responsible for the accumulation of ammonia in the Medullary Interstitium, which, in turn, favors ammonia secretion across the collecting duct. Experimental data indicate that the sodium/hydrogen ion exchanger isoform 4 (NHE4; Scl9a4) is a sodium/ammonia exchanger and plays a major role in this process. Disruption of murine NHE4 leads to metabolic acidosis with inappropriate urinary ammonia excretion and decreases the ability of the TAL to absorb ammonia and to build the corticopapillary ammonia gradient. However, NHE4 does not account for the entirety of ammonia absorption by the TAL, indicating that, at least, one more transporter is involved.