Elevated levels of asymmetric dimethylarginine in chronic heart failure: a pathophysiologic link between oxygen radical load and impaired vasodilator capacity and the therapeutic effect of allopurinol.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide-dependent vasodilation. In 113 patients with chronic heart failure (CHF) and 26 controls, ADMA level was studied in relation to peripheral blood flow and vasodilator capacity. Further, the effects of allopurinol on concentrations of reactive oxygen species (ROS) and ADMA and peripheral vasodilator capacity were tested in a double-blind design. ADMA level was found to be elevated in CHF patients as compared with controls and increased in parallel with New York Heart Association (NYHA) class and exercise capacity (all P < 0.0001). The level of ADMA predicted resting blood flow (P < 0.05) and postischemic vasodilator capacity (P < 0.001). Sixty eight patients died during the follow-up period. The level of ADMA predicted survival after multivariable adjustment (P = 0.04). Allopurinol reduced uric acid (UA) concentration (P < 0.001) and decreased ROS concentration (allantoin, P < 0.01). Allopurinol lowered ADMA concentration (P = 0.02); postischemic vasodilation as well as endothelium-dependent vasodilation (both P < 0.05) improved. ADMA may be a pathophysiologic factor that is modulated by ROS accumulation and contributes to impaired vascular regulation in CHF.
von Haehling
S
S
Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
Bode-Böger
S M
SM
Martens-Lobenhoffer
J
J
Rauchhaus
M
M
Schefold
J C
JC
Genth-Zotz
S
S
Karhausen
T
T
Cicoira
M
M
Anker
S D
SD
Doehner
W
W
D000368:Aged; D000493:Allopurinol / Q000494:pharmacology* / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002908:Chronic Disease; D002956:Citrulline / Q000097:blood; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood; D014664:Vasodilation
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C487735:dimethylarginine; D014527:Uric Acid; D002956:Citrulline; D000493:Allopurinol; D001120:Arginine