Peritoneal dialysis solution attenuates microvascular leukocyte adhesion induced by nitric oxide synthesis inhibition.
In the mesenteric microcirculation, inhibition of nitric oxide (NO) synthesis results in an inflammatory response through increased leukocyte adherence to the microvascular postcapillary venular endothelium. Recent studies have demonstrated that elevated concentrations of endogenous NO synthesis inhibitors are present in renal failure. How peritoneal dialysis solutions may affect leukocyte-endothelial interactions during inflammation induced by NO synthesis inhibition has been previously unknown. Using in vivo intravital microscopy of the rat mesenteric postcapillary venules, microvascular leukocyte adherence was quantitated during baseline conditions in which the mesentery was superfused with a buffer solution, followed by the superfusion of a NO synthesis inhibitor NG-nitro-L-ARGININE methyl ester (L-NAME) added to the buffer, followed by 4.25% Dianeal (4.25% D). When compared to baseline, L-NAME increased the mean number of adherent leukocytes by fivefold (2.2 +/- 0.9 vs 11.6 +/- 3.6 leukocytes/100 microns venule/10 min, p < 0.05), while 4.25% D quickly reversed the L-NAME-induced inflammatory response, returning the number of adherent leukocytes back to baseline values (11.6 +/- 3.6 vs 2.4 +/- 1.3 leukocytes/100 microns venule/ 10 min, p < 0.05). These results confirm that NO synthesis inhibition induces inflammation in mesenteric postcapillary venules. Superfusion of 4.25% D reverses leukocyte adhesion induced by NO synthesis inhibition. Thus, a standard peritoneal dialysis solution (4.25% D) reverses the leukocyte-adhesive effects of NO synthesis inhibition in the mesenteric microcirculation.
White
R
R
Department of Medicine, Overton Brooks VA Medical Center, Shreveport, Louisiana, USA.
Ram
S
S
D000818:Animals; D015314:Dialysis Solutions / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000098:blood supply*; D010538:Peritonitis / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects* / Q000502:physiology
D015314:Dialysis Solutions; D016028:Receptors, Leukocyte-Adhesion; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester