Regulation of NO synthase isoforms in the peritoneum: implications for ultrafiltration failure in peritoneal dialysis.
BACKGROUND
Ultrafiltration (UF) failure often complicates peritoneal dialysis (PD). At least two molecules might be involved in UF failure: aquaporin-1 (AQP1), a water channel thought to be the ultra small pore of the peritoneal membrane (PM), and nitric oxide (NO), which might regulate effective peritoneal surface area and microvascular permeability.


METHODS
The contributions of AQP1 and NO in UF failure were evaluated by combining different experimental approaches. Specific antibodies were used to investigate the expression (immunoblotting) and localization (immunostaining) of AQP1 and NO synthase (NOS) isoforms in the peritoneum, in correlation with: (i) morphometric analyses; (ii) the l-citrulline assay, which specifically measures NOS enzymatic activities; and (iii) permeability parameters across the PM.


RESULTS
AQP1 is located in the endothelium lining peritoneal capillaries, and its expression is remarkably stable in samples ranging from normal to highly inflamed peritoneum and even when transcellular water permeability is absent (loss of sodium sieving). A significant NOS activity, mediated by specific NOS isoforms, can be assayed in the peritoneum. The NOS activity significantly increases in conditions such as peritonitis and long-term PD, and this increase is mirrored by up-regulation of NOS isoforms, as well as angiogenesis and increased endothelial area.


CONCLUSIONS
These data suggest that the NO-mediated increase in effective peritoneal surface area, followed by a dissipation of the osmotic gradient, is a major mechanism accounting for the loss of UF in PD. Other biological consequences of increased NO levels in the peritoneum might include initiation of angiogenesis or modification of functionally important proteins such as AQP1.
Division of Nephrology, Université Catholique de Louvain, Medical School, Brussels, Belgium.
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Devuyst
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Combet
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Cnops
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Stoenoiu
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000378:metabolism; D001789:Blood Group Antigens; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D017211:Treatment Failure; D014462:Ultrafiltration
C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D007527:Isoenzymes; D051398:Aquaporin 1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase