title: Acute administration of L-arginine does not improve arterial endothelial function in chronic renal failure.
abstract: BACKGROUND
  Reduced activity of the nitric oxide (NO) pathway has been implicated in the endothelial dysfunction that occurs in patients with renal failure. NO is generated from L-arginine by NO synthase, and certain uremic toxins including asymmetrical dimethyl-L-arginine (ADMA), inhibit NO synthase and might contribute to endothelial dysfunction. We hypothesized that exogenous L-arginine might improve endothelial function in patients with renal failure by overcoming the effects of uremic toxins.
  
  
  METHODS
  Endothelial function of the forearm resistance vasculature was assessed using plethysmography to measure the dilator response to intra-arterial acetylcholine (25 to 100 nmol/min). Endothelial function of radial and brachial arteries was assessed using vascular ultrasound to measure the dilator response to flow during reactive hyperemia (flow-mediated dilation; FMD). Studies were performed before and after administration of L-arginine by intra-arterial infusion (50 micromol/min) in 8 pre-dialysis patients or by intravenous infusion (10 g) in 18 hemodialysis patients.
  
  
  RESULTS
  Local L-arginine did not improve the dilator response of forearm resistance vessels (AUC 23.1 +/- 6.4 pre, 23.1 +/- 5.1 post; P = 0.9) or FMD of the radial artery (6.5 +/- 1.2% pre, 6.3 +/- 0.8% post; P = 0.8). Systemic L-arginine did not improve FMD of the brachial artery (4.1 +/- 1.1% pre, 3.0 +/- 1.1% post; P = 0.07). These data demonstrate that acute local or systemic administration of L-arginine did not improve endothelial function in resistance or conduit arteries of patients with chronic renal failure.
  
  
  CONCLUSIONS
  The results suggest that competitive inhibition of nitric oxide synthase (NOS) by circulating inhibitors is not the principal explanation for impaired endothelial dilator function in chronic renal failure.
authors.affiliation: Centre for Clinical Pharmacology & Therapeutics, Department of Medicine, University College London, England, United Kingdom. jenny.cross@clara.net
authors.forename: J M
authors.initials: JM
authors.lastname: Cross
authors.forename: A E
authors.initials: AE
authors.lastname: Donald
authors.forename: R
authors.initials: R
authors.lastname: Kharbanda
authors.forename: J E
authors.initials: JE
authors.lastname: Deanfield
authors.forename: R G
authors.initials: RG
authors.lastname: Woolfson
authors.forename: R J
authors.initials: RJ
authors.lastname: MacAllister
mesh_terms: D000328:Adult; D001120:Arginine / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology* / Q000628:therapy; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017534:Radial Artery / Q000503:physiopathology; D012039:Regional Blood Flow / Q000502:physiology; D006435:Renal Dialysis; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase