Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure.
BACKGROUND
Patients with heart failure have reduced peripheral blood flow at rest, during exercise, and in response to endothelium-dependent vasodilators. Nitric oxide formed from L-arginine metabolism in endothelial cells contributes to regulation of blood flow under these conditions. A randomized, double-blind crossover study design was used to determine whether supplemental oral L-arginine can augment peripheral blood flow and improve functional status in patients with moderate to severe heart failure.


RESULTS
Fifteen subjects were given 6 weeks of oral L-arginine hydrochloride (5.6 to 12.6 g/d) and 6 weeks of matched placebo capsules in random sequence. Compared with placebo, supplemental oral L-arginine significantly increased forearm blood flow during forearm exercise, on average from 5.1 +/- 2.8 to 6.6 +/- 3.4 mL. min-1. dL-1 (P < .05). Furthermore, functional status was significantly better on L-arginine compared with placebo, as indicated by increased distances during a 6-minute walk test (390 +/- 91 versus 422 +/- 86 m, P < .05) and lower scores on the Living With Heart Failure questionnaire (55 +/- 28 versus 42 +/- 26, P < .05). Oral L-arginine also improved arterial compliance from 1.99 +/- 0.38 to 2.36 +/- 0.30 mL/mm Hg (P < .001) and reduced circulating levels of endothelin from 1.9 +/- 1.1 to 1.5 +/- 1.1 pmol/L (P < .05).


CONCLUSIONS
Supplemental oral L-arginine had beneficial effects in patients with heart failure. Further studies are needed to confirm the therapeutic potential of supplemental oral L-arginine and to identify mechanisms of action in patients with heart failure.
Rector
T S
TS
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Bank
A J
AJ
Mullen
K A
KA
Tschumperlin
L K
LK
Sih
R
R
Pillai
K
K
Kubo
S H
SH
D000284:Administration, Oral; D000328:Adult; D001120:Arginine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005082:Physical Exertion; D011788:Quality of Life; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase