Dietary supplementation with L-arginine fails to restore endothelial function in forearm resistance arteries of patients with severe heart failure.
OBJECTIVE
We sought to examine the efficacy of dietary supplementation of L-arginine on endothelium-dependent vasodilation in patients with congestive heart failure.


BACKGROUND
Endothelial dysfunction, as evidenced by a diminished response to such vasodilators as acetylcholine, is well defined in patients with heart failure. These responses are improved by intraarterial infusion with L-arginine. Because L-arginine is a semi-essential amino acid, we investigated the effects of dietary L-arginine on endothelium-dependent vasodilation in these patients.


METHODS
Twenty patients with heart failure (New York Heart Association functional class III/IV, mean [+/- SE] age 51.3 +/- 1.7 years) and seven healthy control subjects (mean age 52.6 +/- 3.3 years) were studied. All patients continued taking their usual treatment. Responses to acetylcholine and sodium nitroprusside were determined using forearm plethysmography. Patients with heart failure received either L-arginine (20 g/day every day for 28 days) or placebo (vehicle syrup in equal amounts) in a double-blind protocol. The calculated power of the study was between 62% and 80% to detect a 30% to 40% change in area under the dose-response (forearm vascular resistance) curve.


RESULTS
Responses to acetylcholine, but not to sodium nitroprusside, were significantly attenuated in patients with heart failure compared with control subjects (mean area under curve [AUC], control subjects vs. patients with heart failure: 1,125.4 +/- 164.5 vs. 617.3 +/- 116.6 U, p < 0.05, by Student t test). A significant increase in urea and aspartate transaminase levels in patients receiving active L-arginine treatment was observed. Responses to acetylcholine (AUC; before vs. after L-arginine: 641.5 +/- 126.7 vs. 695.9 +/- 151.9 U) and sodium nitroprusside were not affected by either L-arginine or placebo.


CONCLUSIONS
Endothelial dysfunction was apparent in patients with heart failure despite rigorous vasoactive treatment. Oral administration with L-arginine was ineffective in influencing endothelial function in these patients.
Chin-Dusting
J P
JP
Alfred Hospital and Baker Medical Research Institute, Prahran, Victoria, Australia.
Kaye
D M
DM
Lefkovits
J
J
Wong
J
J
Bergin
P
P
Jennings
G L
GL
D000328:Adult; D001120:Arginine / Q000008:administration & dosage*; D001158:Arteries / Q000503:physiopathology*; D004032:Diet; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014655:Vascular Resistance / Q000187:drug effects*
D001120:Arginine