title: The L-arginine-asymmetric dimethylarginine ratio is strongly related to the severity of chronic heart failure. No effects of exercise training.
abstract: BACKGROUND
  The aim of this study was to relate levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, L-arginine, the substrate for NO generation, and radical oxygen species (ROS) formation to severity of chronic heart failure. The effect of 4 months' group-based exercise training was further investigated.
  
  
  RESULTS
  Eighty patients, aged 45-85 years with New York Heart Association (NYHA) functional class II-IIIb, all on optimal medical treatment, were included. A 6-minute walking test and a bicycle exercise test were performed, and fasting blood samples were collected for determination of N-terminal pro-brain natriuretic peptide (NT-proBNP), L-arginine, ADMA, and ROS generation in circulating leukocytes. ADMA levels were significantly higher in patients in NYHA functional class III versus II (P = .024), and the L-arginine-ADMA ratio was significantly lower (P = .005). After adjustment for covariates, L-arginine-ADMA ratio was associated with 6-minute walking distance (P = .004), exercise capacity (P = .026), and inversely with NT-proBNP (P = .015). Stimulated levels of peroxynitrite on monocytes were inversely related to left ventricular ejection fraction (P = .005). No effect of 4 weeks' exercise training on the measured variables was obtained.
  
  
  CONCLUSIONS
  The strong relationship seen between L-arginine-ADMA ratio, ROS formation in leukocytes, and severity of chronic heart failure contributes to increased knowledge of endothelial dysfunction related to the NO pathway in such patients.
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ulleval, Oslo, Norway. ingebjorg.seljeflot@uus.no
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
authors.forename: Birgitta Blakstad
authors.initials: BB
authors.lastname: Nilsson
authors.forename: Arne S
authors.initials: AS
authors.lastname: Westheim
authors.forename: Vibeke
authors.initials: V
authors.lastname: Bratseth
authors.forename: Harald
authors.initials: H
authors.lastname: Arnesen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism; D004730:Endothelium, Vascular; D005081:Exercise Therapy; D017079:Exercise Tolerance; D005260:Female; D005434:Flow Cytometry; D006305:Health Status Indicators; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology / Q000628:therapy*; D006801:Humans; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000097:blood*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012720:Severity of Illness Index; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase