Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance

J Am Coll Cardiol. 2001 Aug;38(2):499-505. doi: 10.1016/s0735-1097(01)01380-8.

Abstract

Objectives: This study was designed to determine the effect of two weeks' treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatation to acetylcholine, exercise performance and heart rate variability in men with stable angina.

Background: The ratio of plasma L-arginine:ADMA has been proposed as a determinant of endothelium-dependent dilation; dietary supplementation with L-arginine has been shown to improve endothelium-dependent vasodilation and symptoms in some conditions.

Methods: Men (n = 40) with stable angina, at least one epicardial coronary artery with a stenosis >50% and a positive exercise test were randomized to receive L-arginine (15 g daily) or placebo for two weeks according to a double-blind parallel-group design. Plasma L-arginine, ADMA, 8-epi-prostaglandin F2alpha (a marker of oxidative stress) and forearm vasodilator responses to brachial artery infusion of nitroprusside and acetylcholine (+/-L-arginine) were measured. A standard Bruce protocol exercise test was performed before and at the end of the treatment period.

Results: Plasma L-arginine increased after oral L-arginine, whereas ADMA remained unchanged, leading to an increase in the L-arginine/ADMA ratio of 62 +/- 11% (mean +/- SE, p < 0.01). Despite a significant enhancement in acetylcholine response by intra-arterial L-arginine at baseline, this response remained unchanged after oral L-arginine. Measures of oxidative stress and exercise performance after L-arginine/placebo were similar in placebo and active groups.

Conclusions: In men with stable angina, an increase in plasma L-arginine/ADMA ratio after two weeks' oral supplementation with L-arginine is not associated with an improvement in endothelium-dependent vasodilatation, oxidative stress or exercise performance.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Angina Pectoris / blood
  • Angina Pectoris / physiopathology
  • Angina Pectoris / prevention & control*
  • Arginine / administration & dosage
  • Arginine / analogs & derivatives*
  • Arginine / blood*
  • Arginine / pharmacology*
  • Dinoprost / analogs & derivatives
  • Dinoprost / blood
  • Double-Blind Method
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Exercise
  • Exercise Test
  • F2-Isoprostanes
  • Forearm / blood supply
  • Heart Rate / drug effects
  • Humans
  • Injections, Intra-Arterial
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Regional Blood Flow / drug effects
  • Vasodilation / drug effects*

Substances

  • F2-Isoprostanes
  • 8-epi-prostaglandin F2alpha
  • symmetric dimethylarginine
  • N,N-dimethylarginine
  • Arginine
  • Dinoprost