Substrate and inhibitor for nitric oxide synthase during peritoneal dialysis in rabbits

Objective:To investigate the possible influence of nitric oxide (NO) on per itoneal transport during non infected peritoneal dialysis. Design: A chronic peritoneal dialysis model in New Zealand White rabbits (2 624 g; range: 2251 - 3034 g) was used. In 13 rabbits, 250 mg/L L-arginine, a substrate for NO synthesis, was added to 3.86% glucose dialysate. NG-mono methyl-L-arginine (L-NMMA) 25 mg/L, an inhibitor of NO synthase, was added to the dialysate in 10 rabbits. Standard peritoneal permeability analyses i n rabbits (SPAR) were performed to analyze the effects of these interventio ns on solute and fluid transport during 1-hour dwells. The addition of 4.5 mg/L nitroprusside to the dialysate in 5 separate experiments was used for validation of this model. Main outcome: For the transport of urea and creatinine, mass transfer area coefficients (MTACs) were calculated. Furthermore, the glucose absorption, the peritoneal albumin clearance, peritoneal fluid kinetics, and the dialys ate-to-plasma (D/P) ratio of nitrate were calculated. Results: Nitroprusside caused an 86% (48% - 233%) increase in albumin clear ance, which is similar to the nitroprusside-induced increase found in human s. Contrary to the findings in human studies, no effect was found on the cl earances of urea and creatinine, or on peritoneal fluid kinetics. This sugg ests a lower sensitivity of the rabbit peritoneal membrane for the effect o f NO on small-solute transport. L-arginine affected neither the MTACs of ur ea and creatinine, nor the absorption of glucose. Also, peritoneal fluid ki netics were similar. Peritoneal albumin clearance increased 18% (-24% - 609 %). This result resembles the NO-mediated effects of nitroprusside. Additio n of L-NMMA caused no change in the transport rate of small solutes, in alb umin clearance, or in fluid profile. This result suggests that NO synthase is not induced during non infected peritoneal dialysis, which accords with previous studies. Conclusion:This rabbit dialysis model can be used for analyzing the effects of interventions on peritoneal permeability characteristics, although the rabbit peritoneal membrane is probably less sensitive to NO compared to tha t of humans. L-Arginine-induced effects are similar to those of nitroprussi de, which suggests that these effects are possibly mediated by NO. Because L-NMMA did not affect peritoneal transport, it is unlikely that NO is invol ved in the regulation of peritoneal permeability during stable continuous a mbulatory peritonealdialysis.