title: Addition of a nitric oxide inhibitor to a more biocompatible peritoneal dialysis solution in a rat model of chronic renal failure.
abstract: Biocompatible dialysis solutions have been developed to preserve peritoneal membrane morphology and function. Compared with a conventional solution, a combination of glycerol, amino acids, and dextrose in a bicarbonate/lactate buffer (GLAD) led to less peritoneal fibrosis and fewer vessels in a chronic peritoneal exposure model in the rat. However, no concomitant reduction in small-solute transport was observed. We hypothesized that this result could be attributable to peritoneal vasodilation induced by vasoactive substances such as nitric oxide. The aim of the present study was to investigate whether fast transport of small solutes and proteins induced by exposure to GLAD could be influenced by Ngamma -methyl-L-arginine acetate (L-NMMA), an inhibitor of NO. These investigations used our rat model of long-term peritoneal exposure with chronic renal failure. All rats underwent peritoneal catheter implantation and a 70% nephrectomy. Thereafter, the rats were allocated to 3 groups: 16 weeks of peritoneal exposure to GLAD and L-NMMA, to GLAD only, or to buffer (bicarbonate/lactate without any osmotic agent). Afterward, a standard peritoneal permeability analysis adjusted for the rat was performed. Subsequently, the rats were euthanized, and tissue samples were obtained for morphometric determinations. No effect of L-MNNA on the transport of small solutes and proteins was found. Also, no effect on morphology was found. Our findings make it unlikely that NO is directly involved, being more in favor of a direct effect of amino acids on peritoneal transport.
authors.affiliation: Division of Nephrology, Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. marijke.degraaff@amc.uva.nl
authors.forename: Marijke
authors.initials: M
authors.lastname: de Graaff
authors.forename: Anniek
authors.initials: A
authors.lastname: Vlijm
authors.forename: Machteld M
authors.initials: MM
authors.lastname: Zweers
authors.forename: Annemieke M
authors.initials: AM
authors.lastname: Coester
authors.forename: Fréderic
authors.initials: F
authors.lastname: Vandemaele
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Struijk
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Krediet
mesh_terms: D000596:Amino Acids; D000818:Animals; D001672:Biocompatible Materials; D001692:Biological Transport; D005947:Glucose; D005990:Glycerol; D015312:Hemodialysis Solutions / Q000737:chemistry*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000098:blood supply / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D001672:Biocompatible Materials; D015312:Hemodialysis Solutions; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005947:Glucose; D005990:Glycerol