Asymmetric dimethylarginine, L-arginine, and endothelial dysfunction in essential hypertension

J Am Coll Cardiol. 2005 Aug 2;46(3):518-23. doi: 10.1016/j.jacc.2005.04.040.


Objectives: We investigated the relationship between ADMA plasma levels and endothelium-dependent vasodilation in 36 never-treated essential hypertensives and in 8 normotensive healthy subjects.

Background: It has been demonstrated that endothelium-dependent vasodilatation is impaired in essential hypertension. The potential contribution of asymmetric dimethylarginine (ADMA) to endothelial dysfunction of hypertensive humans has received poor attention.

Methods: Endothelial function was measured during intra-arterial infusion of acetylcholine (ACh), alone and during co-infusion of L-arginine, and sodium nitroprusside at increasing doses. Concentrations of ADMA and L-arginine in plasma were measured by high-performance liquid chromatography.

Results: Hypertensive subjects had significantly higher ADMA and L-arginine plasma concentrations than normotensive healthy controls; ACh-stimulated forearm blood flow (FBF) was significantly reduced in hypertensive subjects in comparison to normotensive control subjects (p < 0.0001). Intra-arterial coinfusion of L-arginine induced a further significant enhancement in ACh-stimulated vasodilation in hypertensive patients. In these, ADMA was strongly and inversely associated with the peak increase in FBF. In a multivariate model, only ADMA and L-arginine were independent correlates, accounting for 33.9% and 8.9% of the variability in the peak FBF response to ACh (p < 0.0001), respectively.

Conclusions: The main finding in this study is that in essential hypertensives the L-arginine and endogenous inhibitor of nitric oxide synthase, ADMA, are inversely related to endothelial function.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholine / administration & dosage
  • Arginine / administration & dosage*
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Arginine / metabolism
  • Blood Pressure Determination
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Hypertension / blood*
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Infusions, Intra-Arterial
  • Male
  • Nitroprusside / administration & dosage
  • Probability
  • Reference Values
  • Sensitivity and Specificity
  • Severity of Illness Index


  • Nitroprusside
  • N,N-dimethylarginine
  • Arginine
  • Acetylcholine