Beneficial effects of aminoguanidine on peritoneal microcirculation and tissue remodelling in a rat model of PD.
BACKGROUND
The formation of glucose degradation products (GDPs) and accumulation of advanced glycation end products (AGEs) partly contribute to the bioincompatibility of peritoneal dialysis fluids (PDF). Aminoguanidine (AG) scavenges GDPs and prevents the formation of AGEs.


METHODS
In a peritoneal dialysis (PD) rat model, we evaluated the effects of the addition of AG to the PDF on microcirculation and morphology of the peritoneum, by intravital microscopy and quantitative morphometric analysis.


RESULTS
AG-bicarbonate effectively scavenged different GDPs from PDF. Daily exposure to PDF for 5 weeks resulted in a significant increase in leucocyte rolling in mesenteric venules, which could be reduced for approximately 50% by addition of AG-bicarbonate (P<0.02). Vascular leakage was found in rats treated with PDF/AG-bicarbonate, but not with PDF alone. Evaluation of visceral and parietal peritoneum showed the induction of angiogenesis and fibrosis after PDF instillation. PDF/AG-bicarbonate significantly reduced vessel density in omentum and parietal peritoneum (P<0.04), but not in mesentery. PDF-induced fibrosis was significantly reduced by AG (P<0.02). PDF instillation led to AGE accumulation in mesentery, which was inhibited by supplementation of AG. Since addition of AG-bicarbonate to PDF raised pH from 5.2 to 8.5, a similar experiment was performed with AG-hydrochloride that did not change the fluid acidity. We could reproduce most of the results obtained with AG-bicarbonate; however, AG-hydrochloride induced no microvascular leakage and had a minor effect on angiogenesis.


CONCLUSIONS
The supplementation of either AG reduced a number of PDF-induced alterations in our model, emphasizing the involvement of GDPs and/or AGEs in the PDF-induced peritoneal injury.
Zareie
Mohammad
M
Department of Molecular Cell Biology and Immunology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. m.zareie@vumc.nl.
Tangelder
Geert-Jan
GJ
ter Wee
Piet M
PM
Hekking
Liesbeth H P
LH
van Lambalgen
Anton A
AA
Keuning
Eelco D
ED
Schadee-Eestermans
Inge L
IL
Schalkwijk
Casper G
CG
Beelen
Robert H J
RH
van den Born
Jacob
J
D000818:Animals; D015314:Dialysis Solutions / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005355:Fibrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects; D010530:Peritoneal Dialysis / Q000009:adverse effects / Q000379:methods; D010532:Peritoneal Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010537:Peritoneum / Q000098:blood supply* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
D015314:Dialysis Solutions; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D019001:Nitric Oxide Synthase; C004479:pimagedine