Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral L-arginine in Patients With Heart Failure

Circulation. 1996 Jun 15;93(12):2135-41. doi: 10.1161/01.cir.93.12.2135.

Abstract

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.

Methods and 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Arginine / adverse effects
  • Arginine / blood
  • Arginine / therapeutic use*
  • Cardiac Output, Low / drug therapy*
  • Cardiac Output, Low / physiopathology
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Forearm / blood supply
  • Forearm / physiology
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Physical Exertion
  • Quality of Life
  • Regional Blood Flow / drug effects
  • Vasoconstriction
  • omega-N-Methylarginine / pharmacology

Substances

  • omega-N-Methylarginine
  • Arginine
  • Nitric Oxide Synthase