Acute hyperhomocysteinemia induces microvascular and macrovascular endothelial dysfunction.
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.
Abahji
Thomas N
TN
Department of Vascular Medicine, University of Munich Medical Center, Munich, Germany.
Nill
Lars
L
Ide
Nagatoshi
N
Keller
Christiane
C
Hoffmann
Ulrich
U
Weiss
Norbert
N
D000109:Acetylcholine / Q000008:administration & dosage; D000208:Acute Disease; D000328:Adult; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation
D008715:Methionine; D000109:Acetylcholine