In vivo inhibition of transcellular water channels (aquaporin-1) during acute peritoneal dialysis in rats

1996 ◽  
Vol 271 (6) ◽  
pp. H2254-H2262 ◽  
Author(s):  
O. Carlsson ◽  
S. Nielsen ◽  
el-R. Zakaria ◽  
B. Rippe
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Water Flow ◽  
Peritoneal Cavity ◽  
Critical Role ◽  
Water Channels ◽  
Capillary Endothelium ◽  
Tissue Fixation ◽  
Solute Permeability ◽  
Aquaporin 1

During peritoneal dialysis (PD), a major portion of the osmotically induced water transport to the peritoneum can be predicted to occur through endothelial water-selective channels. Aquaporin-1 (AQP-1) has recently been recognized as the molecular correlate to such channels. Aquaporins can be inhibited by mercurials. In the present study, HgCl2 was applied locally to the peritoneal cavity in rats after short-term tissue fixation, used to protect the tissues from HgCl2 damage. Dianeal (3.86%) was employed as dialysis fluid, 125I-albumin as an intraperitoneal volume marker, and 51Cr-EDTA (constantly infused intravenously) to assess peritoneal small-solute permeability characteristics. Immunocytochemistry and immunoelectron microscopy revealed abundant AQP-1 labeling in capillary endothelium in peritoneal tissues, representing sites for HgCl2 inhibition of water transport. HgCl2 treatment reduced water flow and inhibited the sieving of Na+ without causing any untoward changes in microvascular permeability, compared with that of fixed control rats, in which the peritoneal cavity was exposed to tissue fixation alone. In fixed control rats, the mean intraperitoneal volume (IPV) increased from 20.5 +/- 0.15 to 25.0 +/- 0.52 ml in 60 min, whereas in the HgCl2-treated rats, the increment was only from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+ fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rats the dialysate Na+ concentration remained unchanged between 0 and 40 min, further supporting that water channels had been blocked. Computer simulations of peritoneal transport were compatible with a 66% inhibition of water flow through aquaporins. The observed HgCl2 inhibition of transcellular water channels strongly indicates a critical role of aquaporins in PD and provides evidence that water channels are crucial in transendothelial water transport when driven by crystalloid osmosis.

Aquaporin-1: New Developments and Perspectives for Peritoneal Dialysis

2010 ◽  
Vol 30 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Olivier Devuyst ◽  
Andrea J. Yool
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Water Channel ◽  
Cell Types ◽  
Convective Transport ◽  
Osmotic Gradient ◽  
Pharmacological Agents ◽  
Solute Permeability ◽  
Chemical Screening ◽  
Aquaporin 1

Peritoneal dialysis involves diffusive and convective transport and osmosis through the highly vascularized peritoneal membrane. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore predicted by the model of peritoneal transport. Proof-of-principle studies have shown that upregulation of the expression of AQP1 in peritoneal capillaries results in increased water permeability and ultrafiltration, without affecting the osmotic gradient or small solute permeability. Conversely, studies in Aqp1 mice have shown that haplo-insufficiency for AQP1 results in significant attenuation of water transport. Recent studies have demonstrated that AQP1 is involved in the migration of different cell types, including endothelial cells. In parallel, chemical screening has identified lead compounds that could act as antagonists or agonists of AQPs, with description of putative binding sites and potential mechanisms of gating the water channel. By modulating water transport, these pharmacological agents could have clinically relevant effects in targeting specific tissues or disease states.

Endothelial Glycocalyx and the Peritoneal Barrier

2008 ◽  
Vol 28 (1) ◽  
pp. 6-12 ◽  
Author(s):  
Michael F. Flessner
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Critical Role ◽  
Basic Research ◽  
Endothelial Glycocalyx ◽  
Dialysis Patients ◽  
Solute Transfer ◽  
Histological Studies ◽  
Initial Resistance

Recent advances in the study of the microcirculation have demonstrated the critical role of the endothelial glycocalyx in transcapillary transport from the plasma to the tissue interstitium. Since the capillary wall represents the initial resistance to solute transfer from the plasma through the tissue to the dialysate, the glycocalyx is potentially of major importance to peritoneal dialysis. Inadvertently removed in early histological studies, this thin, delicate layer of glycosaminoglycans and proteoglycans is now recognized as a primary barrier in transendothelial solute and water transport. Subperitoneal endothelia are exposed to inflammation, angiogenesis, and hyperglycemia, which have been shown to affect the layer by increasing permeability. This entity permits new hypotheses concerning the factors that influence the transport characteristics of peritoneal dialysis patients and provides new avenues of basic research into the fundamental mechanisms of alteration of the peritoneal barrier.

Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 knockout mice

1999 ◽  
Vol 276 (1) ◽  
pp. C76-C81 ◽  
Author(s):  
Baoxue Yang ◽  
Hans G. Folkesson ◽  
Jian Yang ◽  
Michael A. Matthay ◽  
Tonghui Ma ◽  
...  
Keyword(s):  
Water Transport ◽  
Peritoneal Cavity ◽  
Knockout Mice ◽  
Fluid Transport ◽  
Water Movement ◽  
Osmotic Gradient ◽  
Half Time ◽  
Aquaporin 1 ◽  
Osmotic Water ◽  
Major Route

Aquaporin-1 (AQP1) water channels are expressed widely in epithelia and capillary endothelia involved in fluid transport. To test whether AQP1 facilitates water movement from capillaries into the peritoneal cavity, osmotically induced water transport rates were compared in AQP1 knockout [(−/−)], heterozygous [(+/−)], and wild-type [(+/+)] mice. In (+/+) mice, RT-PCR showed detectable transcripts for AQP1, AQP3, AQP4, AQP7, and AQP8. Immunofluorescence showed AQP1 protein in capillary endothelia and mesangium near the peritoneal surface and AQP4 in adherent muscle plasmalemma. For measurement of water transport, 2 ml of saline containing 300 mM sucrose (600 mosM) were infused rapidly into the peritoneal cavity via a catheter. Serial fluid samples (50 μl) were withdrawn over 60 min, with albumin as a volume marker. The albumin dilution data showed significantly decreased initial volume influx in AQP1 (−/−) mice: 101 ± 8, 107 ± 5, and 42 ± 4 (SE) μl/min in (+/+), (+/−), and (−/−) mice, respectively [ n = 6–10, P < 0.001, (−/−) vs. others]. Volume influx for AQP4 knockout mice was 100 ± 8 μl/min. In the absence of an osmotic gradient,3H2O uptake [half time = 2.3 and 2.2 min in (+/+) and (−/−) mice, respectively], [14C]urea uptake [half time = 7.9 and 7.7 min in (+/+) and (−/−) mice, respectively], and spontaneous isosmolar fluid absorption from the peritoneal cavity [0.47 ± 0.05 and 0.46 ± 0.04 ml/h in (+/+) and (−/−) mice, respectively] were not affected by AQP1 deletion. Therefore, AQP1 provides a major route for osmotically driven water transport across the peritoneal barrier in peritoneal dialysis.

scholarly journals Aquaporin-1 Facilitates Transmesothelial Water Permeability: In Vitro and Ex Vivo Evidence and Possible Implications in Peritoneal Dialysis

2021 ◽  
Vol 22 (22) ◽  
pp. 12535
Author(s):  
Francesca Piccapane ◽  
Andrea Gerbino ◽  
Monica Carmosino ◽  
Serena Milano ◽  
Arduino Arduini ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Peritoneal Dialysis ◽  
Tight Junctions ◽  
Water Transport ◽  
Water Flux ◽  
Water Channel ◽  
Bathing Solution ◽  
Ussing Chambers ◽  
Aquaporin 1 ◽  
Osmotic Water

We previously showed that mesothelial cells in human peritoneum express the water channel aquaporin 1 (AQP1) at the plasma membrane, suggesting that, although in a non-physiological context, it may facilitate osmotic water exchange during peritoneal dialysis (PD). According to the three-pore model that predicts the transport of water during PD, the endothelium of peritoneal capillaries is the major limiting barrier to water transport across peritoneum, assuming the functional role of the mesothelium, as a semipermeable barrier, to be negligible. We hypothesized that an intact mesothelial layer is poorly permeable to water unless AQP1 is expressed at the plasma membrane. To demonstrate that, we characterized an immortalized cell line of human mesothelium (HMC) and measured the osmotically-driven transmesothelial water flux in the absence or in the presence of AQP1. The presence of tight junctions between HMC was investigated by immunofluorescence. Bioelectrical parameters of HMC monolayers were studied by Ussing Chambers and transepithelial water transport was investigated by an electrophysiological approach based on measurements of TEA+ dilution in the apical bathing solution, through TEA+-sensitive microelectrodes. HMCs express Zo-1 and occludin at the tight junctions and a transepithelial vectorial Na+ transport. Real-time transmesothelial water flux, in response to an increase of osmolarity in the apical solution, indicated that, in the presence of AQP1, the rate of TEA+ dilution was up to four-fold higher than in its absence. Of note, we confirmed our data in isolated mouse mesentery patches, where we measured an AQP1-dependent transmesothelial osmotic water transport. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD through functional expression of the water channel AQP1.

Expression of aquaporin-1 in a long-term peritoneal dialysis patient with impaired transcellular water transport

1999 ◽  
Vol 33 (2) ◽  
pp. 383-388 ◽  
Author(s):  
Eric Goffin ◽  
Sophie Combet ◽  
François Jamar ◽  
Jean-Pierre Cosyns ◽  
Olivier Devuyst
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Dialysis Patient ◽  
Peritoneal Dialysis Patient ◽  
Aquaporin 1

The Importance of the Interstitium in Peritoneal Transport

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 76-79 ◽  
Author(s):  
Michael F. Flessner
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Peritoneal Cavity ◽  
The Body ◽  
Fluid Loss ◽  
Blood Capillary ◽  
Dialysis Fluid ◽  
Peritoneal Dialysis Fluid ◽  
Capillary Exchange ◽  
Additional Barrier

The peritoneal capillary exchange vessels are located within all the tissues which surround the peritoneal cavity and are separated from the peritoneal dialysis fluid by the tissue interstitium. The interstitium adds an additional barrier to transcapillary transport resistance and slows the diffusion of solutes from the blood to the dialysis fluid. The interstitium also alters the pressure environment of the blood capillary and has profound effects on water transport, causing fluid loss from the cavity to the body during dialysis.

scholarly journals Secretin Promotes Osmotic Water Transport in Rat Cholangiocytes by Increasing Aquaporin-1 Water Channels in Plasma Membrane

1997 ◽  
Vol 272 (20) ◽  
pp. 12984-12988 ◽  
Author(s):  
Raul A. Marinelli ◽  
Linh Pham ◽  
Peter Agre ◽  
Nicholas F. LaRusso
Keyword(s):  
Plasma Membrane ◽  
Water Transport ◽  
Water Channels ◽  
Aquaporin 1 ◽  
Osmotic Water

scholarly journals A Mathematical Model of Solute Coupled Water Transport in Toad Intestine Incorporating Recirculation of the Actively Transported Solute

2000 ◽  
Vol 116 (2) ◽  
pp. 101-124 ◽  
Author(s):  
Erik Hviid Larsen ◽  
Jakob Balslev Sørensen ◽  
Jens Nørkær Sørensen
Keyword(s):  
Mathematical Model ◽  
Water Transport ◽  
Water Flow ◽  
Flux Ratio ◽  
Hydraulic Conductance ◽  
Paracellular Pathway ◽  
Solute Flux ◽  
Energetic Efficiency ◽  
Solvent Drag ◽  
Solute Permeability

A mathematical model of an absorbing leaky epithelium is developed for analysis of solute coupled water transport. The non-charged driving solute diffuses into cells and is pumped from cells into the lateral intercellular space (lis). All membranes contain water channels with the solute passing those of tight junction and interspace basement membrane by convection-diffusion. With solute permeability of paracellular pathway large relative to paracellular water flow, the paracellular flux ratio of the solute (influx/outflux) is small (2–4) in agreement with experiments. The virtual solute concentration of fluid emerging from lis is then significantly larger than the concentration in lis. Thus, in absence of external driving forces the model generates isotonic transport provided a component of the solute flux emerging downstream lis is taken up by cells through the serosal membrane and pumped back into lis, i.e., the solute would have to be recirculated. With input variables from toad intestine (Nedergaard, S., E.H. Larsen, and H.H. Ussing, J. Membr. Biol. 168:241–251), computations predict that 60–80% of the pumped flux stems from serosal bath in agreement with the experimental estimate of the recirculation flux. Robust solutions are obtained with realistic concentrations and pressures of lis, and with the following features. Rate of fluid absorption is governed by the solute permeability of mucosal membrane. Maximum fluid flow is governed by density of pumps on lis-membranes. Energetic efficiency increases with hydraulic conductance of the pathway carrying water from mucosal solution into lis. Uphill water transport is accomplished, but with high hydraulic conductance of cell membranes strength of transport is obscured by water flow through cells. Anomalous solvent drag occurs when back flux of water through cells exceeds inward water flux between cells. Molecules moving along the paracellular pathway are driven by a translateral flow of water, i.e., the model generates pseudo-solvent drag. The associated flux-ratio equation is derived.

scholarly journals Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal Membrane

2018 ◽  
Vol 29 (7) ◽  
pp. 1875-1886 ◽  
Author(s):  
Johann Morelle ◽  
Amadou Sow ◽  
Charles-André Fustin ◽  
Catherine Fillée ◽  
Elvia Garcia-Lopez ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Water Flow ◽  
Molecular Mechanisms ◽  
Experimental Models ◽  
Peritoneal Membrane ◽  
Aquaporin 1 ◽  
Dialysis Solution ◽  
Osmotic Water ◽  
Osmotic Agents

Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated.Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin.ResultsIn silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone.Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.

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