title: Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance.
abstract: OBJECTIVE
  This study was designed to determine the effect of two weeks' treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatation to acetylcholine, exercise performance and heart rate variability in men with stable angina.
  
  
  BACKGROUND
  The ratio of plasma L-arginine:ADMA has been proposed as a determinant of endothelium-dependent dilation; dietary supplementation with L-arginine has been shown to improve endothelium-dependent vasodilation and symptoms in some conditions.
  
  
  METHODS
  Men (n = 40) with stable angina, at least one epicardial coronary artery with a stenosis >50% and a positive exercise test were randomized to receive L-arginine (15 g daily) or placebo for two weeks according to a double-blind parallel-group design. Plasma L-arginine, ADMA, 8-epi-prostaglandin F2alpha (a marker of oxidative stress) and forearm vasodilator responses to brachial artery infusion of nitroprusside and acetylcholine (+/-L-arginine) were measured. A standard Bruce protocol exercise test was performed before and at the end of the treatment period.
  
  
  RESULTS
  Plasma L-arginine increased after oral L-arginine, whereas ADMA remained unchanged, leading to an increase in the L-arginine/ADMA ratio of 62 +/- 11% (mean +/- SE, p < 0.01). Despite a significant enhancement in acetylcholine response by intra-arterial L-arginine at baseline, this response remained unchanged after oral L-arginine. Measures of oxidative stress and exercise performance after L-arginine/placebo were similar in placebo and active groups.
  
  
  CONCLUSIONS
  In men with stable angina, an increase in plasma L-arginine/ADMA ratio after two weeks' oral supplementation with L-arginine is not associated with an improvement in endothelium-dependent vasodilatation, oxidative stress or exercise performance.
authors.affiliation: Cardiothoracic Centre, St. Thomas' Hospital, London, United Kingdom.
authors.forename: H A
authors.initials: HA
authors.lastname: Walker
authors.forename: E
authors.initials: E
authors.lastname: McGing
authors.forename: I
authors.initials: I
authors.lastname: Fisher
authors.forename: R H
authors.initials: RH
authors.lastname: Böger
authors.forename: S M
authors.initials: SM
authors.lastname: Bode-Böger
authors.forename: G
authors.initials: G
authors.lastname: Jackson
authors.forename: J M
authors.initials: JM
authors.lastname: Ritter
authors.forename: P J
authors.initials: PJ
authors.lastname: Chowienczyk
mesh_terms: D000284:Administration, Oral; D000787:Angina Pectoris / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D015444:Exercise; D005080:Exercise Test; D028441:F2-Isoprostanes; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D028441:F2-Isoprostanes; C075750:8-epi-prostaglandin F2alpha; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D015237:Dinoprost