title: Asymmetrical dimethylarginine plasma concentrations are related to basal nitric oxide release but not endothelium-dependent vasodilation of resistance arteries in peritoneal dialysis patients.
abstract: Vascular dysfunction in chronic renal failure may be linked to reduced nitric oxide (NO) bioactivity and increased circulating concentrations of the endogenous NO synthase inhibitor asymmetrical dimethyl L-arginine (ADMA). The association between ADMA and basal endothelial NO release and endothelium-dependent vasodilation in resistance arteries of chronic renal failure patients is unknown. Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine, the endothelium-independent vasodilator nitroglycerine, and the endothelium-dependent vasoconstrictor N(G)-monomethyl-L-arginine (L-NMMA) were assessed in 37 peritoneal dialysis patients. L-arginine and ADMA plasma concentrations were measured by HPLC. ADMA (mean +/- SEM: 0.68 +/- 0.02 micromol/L) was associated with basal forearm blood flow (r = -0.33; P < 0.05) and L-NMMA induced vasoconstriction (r = -0.55; P < 0.0005), but not with dilator effects of acetylcholine or nitroglycerine. L-arginine (68 +/- 3 micromol/L) tended to correlate with acetylcholine-induced vasodilation (r = 0.32; P = 0.05) but was not associated with other parameters. ADMA is related to basal but not to acetylcholine-stimulated NO bioactivity in patients on peritoneal dialysis. Impaired endothelium-dependent vasodilation found in chronic renal failure is not explained by elevated circulating NO synthase inhibitors in renal failure.
authors.affiliation: Medical University Vienna, Department of Clinical Pharmacology, Division of Nephrology and Dialysis, AKH-Wien, Währinger Gürtel 18-20, Vienna, A-1090 Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Mittermayer
authors.forename: Georg
authors.initials: G
authors.lastname: Schaller
authors.forename: Johannes
authors.initials: J
authors.lastname: Pleiner
authors.forename: Andreas
authors.initials: A
authors.lastname: Vychytil
authors.forename: Gere
authors.initials: G
authors.lastname: Sunder-Plassmann
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001158:Arteries / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010530:Peritoneal Dialysis; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase