PMID- 21300303 OWN - NLM STAT- MEDLINE DCOM- 20110602 LR - 20161125 IS - 1532-8414 (Electronic) IS - 1071-9164 (Linking) VI - 17 IP - 2 DP - 2011 Feb TI - The L-arginine-asymmetric dimethylarginine ratio is strongly related to the severity of chronic heart failure. No effects of exercise training. PG - 135-42 LID - 10.1016/j.cardfail.2010.09.003 [doi] AB - 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. METHOD AND 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Seljeflot, Ingebjorg AU - Seljeflot I AD - Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ulleval, Oslo, Norway. ingebjorg.seljeflot@uus.no FAU - Nilsson, Birgitta Blakstad AU - Nilsson BB FAU - Westheim, Arne S AU - Westheim AS FAU - Bratseth, Vibeke AU - Bratseth V FAU - Arnesen, Harald AU - Arnesen H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101028 PL - United States TA - J Card Fail JT - Journal of cardiac failure JID - 9442138 RN - 0 (Peptide Fragments) RN - 0 (Reactive Oxygen Species) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 63CV1GEK3Y (N,N-dimethylarginine) RN - 94ZLA3W45F (Arginine) RN - EC 1.14.13.39 (Nitric Oxide Synthase) SB - IM MH - Aged MH - Aged, 80 and over MH - Arginine/*analogs & derivatives/*blood/metabolism MH - Endothelium, Vascular MH - *Exercise Therapy MH - Exercise Tolerance MH - Female MH - Flow Cytometry MH - Health Status Indicators MH - Heart Failure/drug therapy/enzymology/*therapy MH - Humans MH - Leukocytes MH - Male MH - Middle Aged MH - Natriuretic Peptide, Brain/*blood MH - Nitric Oxide Synthase/antagonists & inhibitors MH - Peptide Fragments/*blood MH - Reactive Oxygen Species/metabolism MH - Severity of Illness Index MH - Stroke Volume MH - Treatment Outcome MH - Ventricular Function, Left EDAT- 2011/02/09 06:00 MHDA- 2011/06/03 06:00 CRDT- 2011/02/09 06:00 PHST- 2010/04/12 00:00 [received] PHST- 2010/08/20 00:00 [revised] PHST- 2010/09/24 00:00 [accepted] PHST- 2011/02/09 06:00 [entrez] PHST- 2011/02/09 06:00 [pubmed] PHST- 2011/06/03 06:00 [medline] AID - S1071-9164(10)01127-9 [pii] AID - 10.1016/j.cardfail.2010.09.003 [doi] PST - ppublish SO - J Card Fail. 2011 Feb;17(2):135-42. doi: 10.1016/j.cardfail.2010.09.003. Epub 2010 Oct 28.