Regulation of NO synthase isoforms in the peritoneum: implications for ultrafiltration failure in peritoneal dialysis

Background. Ultrafiltration (UF) failure often complicates peritoneal dialy sis (PD). At least two molecules might be involved in UF failure: aquaporin -1 (AQP1), a water channel thought to be the ultrasmall pore of the periton eal membrane (PM), and nitric oxide (NO), which might regulate effective pe ritoneal surface area and microvascular permeability. Methods. The contributions of AQP1 and NO in UF failure were evaluated by c ombining different experimental approaches. Specific antibodies were used t o investigate the expression (immunoblotting) and localization (immunostain ing) of AQP1 and NO synthase (NOS) isoforms in the peritoneum, in correlati on with: (i) morphometric analyses; (ii) the L-citrulline assay, which spec ifically measures NOS enzymatic activities; and (iii) permeability paramete rs 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 h ighly inflamed peritoneum and even when transcellular water permeability is absent (loss of sodium sieving). A significant NOS activity, mediated by s pecific NOS isoforms, can be assayed in the peritoneum. The NOS activity si gnificantly increases in conditions such as peritonitis and long-term PD, a nd this increase is mirrored by up-regulation of NOS isoforms, as well as a ngiogenesis 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 initia tion of angiogenesis or modification of functionally important proteins suc h as AQP1.