The L-Arginine–Asymmetric Dimethylarginine Ratio Is Strongly Related to the Severity of Chronic Heart Failure. No Effects of Exercise Training

BackgroundThe 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 ResultsEighty 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.ConclusionsThe 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.