Inhibition of nitric oxide synthase reverses changes in peritoneal permeability in a rat model of acute peritonitis

Ferrier, M.; Combet, Sophie; Landschoot, Mieke Van; Stoenoiu, Maria; Cnops, Yvette; Lameire, Norbert; Devuyst, Olivier

doi:10.1046/j.1523-1755.2001.00050.x

Cited by 47 publications

(52 citation statements)

References 21 publications

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“…The C57 BL/6J eNOS ϩ/ϩ (wild-type [WT]) and eNOS Ϫ/Ϫ (knockout [KO]) mice were generated as described previously (17) and obtained from the Jackson Laboratory (Bar Harbor, ME). Male Wistar rats, aged 8 to 10 wk, were used for comparative studies (6,10,14). All animals had access to appropriate standard diet and tap water ad libitum.…”

Section: Animals Experimental Groups and Acute Peritonitis Modelmentioning

confidence: 99%

“…In a second series of experiments, 11 pairs of eNOS WT and KO mice matched for age were investigated in control conditions (n ϭ 5) or after acute peritonitis (n ϭ 6). Acute peritonitis was generated by insertion of a peritoneal catheter as described previously (6,14). At day 0, mice were anesthetized with ketamine (100 mg/kg subcutaneously; Merial, Brussels, Belgium) and xylazine (10 mg/kg subcutaneously; Bayer, Brussels, Belgium).…”

Section: Animals Experimental Groups and Acute Peritonitis Modelmentioning

confidence: 99%

“…A peritoneal equilibration test similar to that used in rat (6,14) was used to investigate peritoneal permeability parameters in mice. After anesthesia with ketamine and xylazine, mice were placed on a thermopad at 37°C.…”

Section: Peritoneal Permeability Measurement and Tissue Samplingmentioning

confidence: 99%

“…Urea, glucose, sodium, and total protein were assayed using a Kodak Ektachem DT60 II and DTE II analyser (Eastman Kodak Company, Rochester, NY). PD parameters were also obtained in rats, using 15 ml of standard dialysate containing either 3.86% glucose (n ϭ 6) or 7% glucose (n ϭ 6) as described previously (6,14). At the end of the dwell, animals were killed and peritoneum samples were processed for fixation and protein extraction as described previously (6,10,14).…”

Section: Peritoneal Permeability Measurement and Tissue Samplingmentioning

confidence: 99%

“…In control conditions, NOS inhibitors showed no effect on peritoneal permeability parameters (12,13). In acute peritonitis, a condition characterized by increased NOS activity as a result of upregulation of eNOS and inducible NOS (iNOS) (6,14), addition of the NOS inhibitor N G -nitro-L-arginine methyl ester (L-NAME) to the dialysate resulted in a significant reduction of peritoneal permeability with an improvement of UF (14).…”

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confidence: 99%

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Mice that Lack Endothelial Nitric Oxide Synthase Are Protected against Functional and Structural Modifications Induced by Acute Peritonitis

Ni¹,

Moulin²,

Gianello³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Pharmacologic studies suggest that the release of nitric oxide (NO) by endothelial NO synthase (eNOS) contributes to functional alterations of the peritoneal membrane (PM) induced by acute peritonitis. In this study, peritoneal permeability parameters in a mouse model of peritoneal dialysis were characterized, and the effects of eNOS deletion on the PM structure and permeability at baseline and after catheter-induced bacterial peritonitis were examined. Exposure of C57BL/6 mice to standard dialysate yielded a transport of urea and glucose, a sodium sieving, and a net ultrafiltration that were remarkably similar to the values obtained in rats. In comparison with controls, mice with catheter-induced peritonitis were characterized by structural changes in the PM (mononuclear cells infiltrate, vascular proliferation), upregulation of endothelial and inducible NOS, increased permeability for urea and glucose, decreased ultrafiltration, and increased protein loss in the dialysate. Comparison of eNOS wild-type and knockout mice revealed that the permeability modifications and structural changes induced by acute peritonitis were significantly reversed in eNOS knockout mice, resulting in a net increase in ultrafiltration. In contrast, the deletion of eNOS in mouse peritoneum was not reflected by permeability modifications or structural changes at baseline. These results are the first to take advantage of a knockout mouse model to demonstrate directly the crucial importance of eNOS in the permeability and structural modifications caused by acute peritonitis. The characterization of this mouse model suggests that genetically modified mice represent useful tools to investigate the molecular bases of the peritoneal changes during peritoneal dialysis.Despite technological advances and accumulating clinical experience, acute peritonitis remains the most frequent and serious complication of peritoneal dialysis (PD) (1). Understanding the molecular mechanisms that operate in acute peritonitis thus is an essential goal to reduce the functional and structural changes associated with the condition. Studies in rat and rabbit models of PD have demonstrated that transport across the peritoneal membrane (PM) depends on (1) the intrinsic permeability to each solute and (2) the effective peritoneal surface area (EPSA) reflecting the number of perfused capillaries within the peritoneum (2). The capillary endothelium, which expresses both the endothelial nitric oxide (NO) synthase (eNOS) and the water channel aquaporin-1 (AQP1), constitutes the major barrier for solutes and water transport during PD (3,4). Acute peritonitis is characterized by an increased EPSA, with increased permeability for small solutes and glucose, a faster-than-normal dissipation of the osmotic gradient, a decrease of free-water permeability, and a loss of ultrafiltration (UF) (5,6). These modifications are associated with mononuclear cell infiltrate and vascular proliferation within the PM (6).During the past decade, NO has emerged as a crucial mediator in...

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Section: Animals Experimental Groups and Acute Peritonitis Modelmentioning

confidence: 99%

Section: Animals Experimental Groups and Acute Peritonitis Modelmentioning

confidence: 99%

Section: Peritoneal Permeability Measurement and Tissue Samplingmentioning

confidence: 99%