Acute hyperhomocysteinemia induces microvascular and macrovascular endothelial dysfunction

Arch Med Res. 2007 May;38(4):411-6. doi: 10.1016/j.arcmed.2007.01.004.


Background: Hyperhomocysteinemia (Hhcy) has been shown to induce endothelial dysfunction due to a decrease in bioavailable nitric oxide (NO) by increased vascular oxidant stress. This can be detected as an impairment of endothelium-dependent vasodilation in conductance arteries, like brachial or coronary arteries. The effect of Hhcy on endothelial function (EF) in small resistance vessels that critically determine organ perfusion, however, has not been studied systematically in humans. Therefore, we simultaneously determined macro- and microvascular EF in 11 healthy subjects before and during acute Hhcy induced by an oral methionine challenge.

Methods: Macrovascular EF was determined by measuring endothelium-dependent flow-mediated vasodilation of the brachial artery by vascular ultrasound and microvascular EF by measuring skin perfusion during iontophoresis of acetylcholine using laser Doppler fluxmetry.

Results: Oral methionine significantly increased homocysteine levels by about 5.1-fold. Acute Hhcy leads to a significant decrease in flow-mediated vasodilation of the brachial artery from 8.1 +/- 0.5% to 3.6 +/- 0.6% and to a significant decrease in the ratio of acetylcholine-stimulated vs. baseline laser Doppler flow in the forearm skin (from 9.2 +/- 1.0- to 7.8 +/- 1.3-fold).

Conclusions: Acute Hhcy impairs macro- as well as microvascular (EF) in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage
  • Acute Disease
  • Adult
  • Brachial Artery / drug effects
  • Brachial Artery / physiopathology*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Hyperhomocysteinemia / chemically induced
  • Hyperhomocysteinemia / physiopathology*
  • Male
  • Methionine / administration & dosage
  • Microcirculation / drug effects
  • Microcirculation / physiopathology
  • Skin / blood supply*
  • Vasodilation


  • Methionine
  • Acetylcholine