Aquaporin-1 and endothelial nitric oxide synthase expression in capillary endothelia of human peritoneum

Devuyst, Olivier; Nielsen, Søren; Cosyns, Jean Pierre; Smith, Barbara L.; Agre, Peter; Squifflet, Jean; Pouthier, Dominique; Goffin, Éric

doi:10.1152/ajpheart.1998.275.1.h234

Cited by 72 publications

(89 citation statements)

References 27 publications

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“…d. In a conventional Icodextrin PD solution, ~25-30% of the molecules (~3 mM) act as a colloid, implying a reflection coefficient close to unity. It should be noted that 3 mM of high MW icodextrin will produce a colloid osmotic pressure of ~58 mmHg (3 x 19.3 mmHg), which is sufficient to counteract the plasma colloid osmotic pressure (22)(23)(24)(25)(26) exerted by approximately 1 mM of negatively charged plasma proteins. Note, that the partitioning of fluid flows among the different porous pathways in the TPM is now almost identical to that in the peritoneum occurring during high net UF conditions in the absence of crystalloid osmotic forces.…”

Section: Discussionmentioning

confidence: 99%

“…2A-B). Aquaporin-1 is a water-specific membrane channel, impermeable to urea and glycerol, that is distributed in many different cell types including the endothelium lining peritoneal capillaries and post-capillary venules (24). AQP1 is organized as a homotetramer, with each monomer containing six membrane-spanning 〈-helices forming a right-handed twisted arrangement surrounding a hourglass-shaped central pore.…”

Section: Aquaporin-1 Is the Ultrasmall Pore Of The Peritoneal Membranementioning

confidence: 99%

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Water transport across the peritoneal membrane

Devuyst

Rippe

2014

Kidney International

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Peritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a three-pore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haploinsufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small-solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open-state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated. ABSTRACTPeritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a threepore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haplo-insufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated.The development of peritoneal dialysis (PD) as a successful therapy for patients with end stage renal disease has been paralleled by the need to understand the transport mechanisms operating in the peritoneal membrane. Functional alterations in the dialysis capacity of the...

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Section: Discussionmentioning

confidence: 99%

Section: Aquaporin-1 Is the Ultrasmall Pore Of The Peritoneal Membranementioning

confidence: 99%

Water transport across the peritoneal membrane

Devuyst

Rippe

2014

Kidney International

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“…33,54,55 We used the following antibodies: mouse monoclonal anti-human eNOS (Transduction Laboratories, Lexington, KY), purified rabbit anti-vWf (DAKO, Glostrup, Denmark), monoclonal anti-human VEGF (Santa Cruz Biotechnology, Santa Cruz, CA), and polyclonal rabbit anti-human AQP1 (Chemicon International, Temecula, CA).…”

Section: Peritoneal Sampling and Processingmentioning

confidence: 99%

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

Morelle

Sow

Hautem

et al. 2015

Journal of the American Society of Nephrology

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105

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Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.

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“…Recent research conducted in peritoneum from humans and rats indicated that endothelial NOS underwent a considerable upregulation in cases of peritoneal inflammation or acute peritonitis (7,46). Another study argued that nitric oxide might be protective of fibrosis, while constant inhibition of NOS exacerbated fibrosis in rats (24).…”

Section: Türk Nefroloji Diyaliz Ve Transplantasyon Dergisi Turkish Nementioning

confidence: 99%

Effects of Mycophenolate Mofetil and Rapamycin on Peritoneal Fibrosis in an Experimental Model of Peritoneal Dialysis

Dursun¹,

Noyan²,

Erdoğan³

et al. 2015

Turk Neph Dial Transpl

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OBJEcTIVE: This study aimed to investigate the effect of mycophenolate mofetil and rapamycin on peritoneal function and morphology in a rat model of experimental peritoneal dialysis. MATERIAL and METHODS:A total of 60 male Albino rats (Wistar strain) were equally divided into four groups as follows: Mycophenolate mofetil group (MMFG), rapamycin group (RAPG) and no-treatment group (NTG) receiving 15 mL 3.86% glucose solution, and control group (CG) receiving daily intraperitoneal injection of 15 mL normal saline. Mycophenolate mofetil and rapamycin were administered orally via daily gastric gavage in MMFG and RAPG. We conducted one-hour peritoneal equilibration tests at 8 weeks, measuring ultrafiltration, serum and dialysate growth factors and cytokines. Peritoneal membrane morphology was examined under the light microscope. RESULTS:Compared to controls, levels of serum and dialysate vascular endothelial growth factor were significantly higher in NTG (p<0.05), but they did not differ significantly in MMFG and RAPG (p>0.05). Net ultrafiltration was significantly higher in MMFG than in NTG (p<0.05). A significant decline was detected in the number of mesothelial, inflammatory and fibroblast cells and peritoneal membrane thickness in MMFG, as compared with NTG. cONcLUSION:We conclude that peritoneal functions such as ultrafiltration capacity can be protected by treatment with MMF and RAP, as they produce a membrane-protective effect in peritoneal dialysis. KEY wORDS:Experimental peritoneal dialysis, Mycophenolate mofetil, Peritoneal fibrosis, Rapamycin, Rat ÖZ AMAÇ: Çalışmanın amacı deneysel bir sıçan periton diyaliz modelinde mikofenolat mofetil ve rapamisinin periton fonksiyonu ve morfolojisi üzerine etkisini araştırmaktır. GEREÇ ve YÖNTEMLER:Wistar-Albino 60 sıçan 4 eşit gruba ayrıldı: Mikofenolat mofetil grubu (MMFG), rapamisin grubu (RAPG) ve tedavi almayan grubu (NTG) %3,86 glikozlu solüsyonundan 15 mL ve kontrol grubu (CG) normal izotonik sıvıdan 15 mL günde tek doz intraperitoneal enjeksiyonla aldı. MMFG ve RAPG günlük gastrik gavajla sırasıyla mikofenolat mofetil ve rapamisin aldılar. Sekiz hafta sonunda 1 saatlik bir periton eşitleme testi yapıldı. Ultrafiltrasyon, serum ve diyalizatta büyüme faktörleri ve sitokinler ölçüldü. Periton membran morfolojisi ışık mikroskopisi ile değerlendirildi.BULGULAR: Serum ve diyalizat vasküler endotelyal büyüme faktör düzeyleri CG ile karşılaştırıl-dığında NTG da anlamlı oranda daha yüksek saptandı (p<0,05), fakat MMFG ve RAPG gruplarında anlamlı fark saptanmadı (p>0,05). Net ultrafiltrasyon NTG'la karşılaştırıldığında MMFG'da anlamlı oranda daha yüksekti (p<0,05). NTG ile karşılaştırıldığında mezotelyal, inflamatuvar ve fibroblast hücre sayısı ile periton membran kalınlığı MMFG'da anlamlı oranda daha düşük saptandı. SONUÇ:Ultrafiltrasyon gibi periton fonksiyonlarının MMF ve RAP ile korunduğu ve bu ilaçların periton diyalizinde periton membranını koruyucu etkiye sahip oldukları sonucuna vardık.

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Aquaporin-1 and endothelial nitric oxide synthase expression in capillary endothelia of human peritoneum

Cited by 72 publications

References 27 publications

Water transport across the peritoneal membrane

Water transport across the peritoneal membrane

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

Effects of Mycophenolate Mofetil and Rapamycin on Peritoneal Fibrosis in an Experimental Model of Peritoneal Dialysis

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Aquaporin-1 and endothelial nitric oxide synthase expression in capillary endothelia of human peritoneum

Cited by 72 publications

References 27 publications

Water transport across the peritoneal membrane

Water transport across the peritoneal membrane

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

Effects of Mycophenolate Mofetil and Rapamycin on Peritoneal Fibrosis ￼in an Experimental Model of Peritoneal Dialysis

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Effects of Mycophenolate Mofetil and Rapamycin on Peritoneal Fibrosis in an Experimental Model of Peritoneal Dialysis