Hemodialysis and L-arginine, but not D-arginine, correct renal failure-associated endothelial dysfunction.
In end-stage renal failure (ESRF) symptomatic hemodialysis-related hypotension may prevent effective provision of renal replacement therapy. Endogenous inhibitors of nitric oxide synthase accumulate in ESRF and are cleared by dialysis. We, therefore, hypothesised that removal of these inhibitors by hemodialysis would increase endothelial nitric oxide generation and promote venodilation. In vivo responses of norepinephrine preconstricted dorsal hand veins to locally active doses of acetylcholine (an activator of nitric oxide synthase) and glyceryl trinitrate (GTN; a nitric oxide donor) were examined in patients undergoing maintenance hemodialysis for ESRF and in healthy age- and sex-matched controls. Patient studies were undertaken before and after dialysis. Studies before dialysis were repeated with co-infusion of either L-arginine or its inactive enantiomer D-arginine. Venodilation in response to acetylcholine was impaired before, and corrected by, dialysis whereas venodilation to GTN was similar before and after dialysis. Venodilation in response to acetylcholine before dialysis was restored by co-infusion of L- but not D-arginine. Therefore, patients with ESRF undergoing hemodialysis have impaired acetylcholine-mediated venodilation consistent with the accumulation in ESRF of functionally important inhibitors of nitric oxide synthase that are cleared by dialysis.
Hand
M F
MF
Clinical Pharmacology Unit & Research Centre, University of Edinburgh, Western General Hospital, Scotland, United Kingdom.
Haynes
W G
WG
Webb
D J
DJ
D000328:Adult; D000368:Aged; D001120:Arginine / Q000097:blood* / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002802:Cholinesterases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009638:Norepinephrine / Q000008:administration & dosage; D006435:Renal Dialysis; D013237:Stereoisomerism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014680:Veins / Q000187:drug effects
D014662:Vasoconstrictor Agents; D001120:Arginine; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D002802:Cholinesterases; D009638:Norepinephrine