Peritoneal dialysis solutions reverse the hemodynamic effects of nitric oxide synthesis inhibitors.
Nitric oxide (NO) synthesis is inhibited by a variety of L-arginine analogs including NG-nitro-L-arginine methyl ester (L-NAME) and NG NG-dimethylarginine (ADMA). ADMA is present in elevated concentrations in renal failure and potentially could alter microcirculatory hemodynamics during peritoneal dialysis (PD). This investigation utilized the techniques of intravital microscopy to quantitate the mesenteric arteriolar hemodynamic effects of PD solutions during NO synthesis inhibition. L-NAME (100 microns) produced maximum arteriolar vasoconstriction to 74% of baseline diameter (19.9 +/- 2.2 vs. 26.9 +/- 1.4 microns, P < 0.001, N = 10) and ADMA (100 microns) to 68% (20.5 +/- 2.5 vs. 30.1 +/- 2.0 microns, P < 0.01, N = 6). L-NAME decreased red blood cell velocity to 44% of baseline velocity (3.8 +/- 0.8 vs. 8.5 +/- 1.1 mm/second, P < 0.001) and ADMA to 52% (5.1 +/- 1.1 vs. 9.8 +/- 0.9 mm/second, P < 0.01, N = 6). Despite NO synthesis inhibition, standard PD solutions reversed these hemodynamic effects with both 1.5% and 4.25% Dianeal (Baxter) rapidly reversing the vasoconstriction and restoring blood flow back to baseline values. When Dianeal and L-NAME were simultaneously superfused, no L-NAME induced vasoconstriction occurred and Dianeal maintained vasodilatory properties despite L-NAME (P < 0.01, N = 5). This investigation reaffirms that basal levels of NO are important in maintaining normal hemodynamics in the mesenteric microcirculation. Reversal of the L-NAME induced arteriolar hemodynamic effects by Dianeal suggests that the endogenous NO synthesis inhibitor ADMA has no significant effects in the regulation of the mesenteric microvascular arteriolar hemodynamics during PD. Since these PD solutions remain vasoactive despite NO synthesis inhibition, this suggests that these PD solutions possess vasoactive properties primarily through a NO independent mechanism.
White
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R
Department of Medicine, Louisiana State University Medical Center, Shreveport, USA.
Barefield
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D
Ram
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S
Work
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015314:Dialysis Solutions / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010530:Peritoneal Dialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
D015314:Dialysis Solutions; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester