Acute hyperhomocysteinaemia affects pulse pressure but not microvascular vasodilator function.
OBJECTIVE
Raised homocysteine (hcy) levels are associated with premature coronary artery disease, but the underlying vascular mechanism and the extent to which hcy affects small vessel vasodilator responses (especially non-nitric oxide mediated pathways) are unclear.


METHODS
This double-blind, placebo-controlled crossover study in 14 healthy male subjects evaluated the effects of single-dose oral methionine 15 g (to induce acute hyperhomocysteinaemia) on cutaneous microvascular vasodilator responses to incremental-dose iontophoretic administration of acetylcholine (Ach) and sodium nitroprusside (SNP) using laser Doppler fluximetry (LDF), and the effects on von Willibrand factor (vWF) levels and systemic haemodynamics.


RESULTS
Methionine administration produced a three fold rise in plasma hcy levels at 8 h, which was accompanied by a significant increase in pulse pressure (53 vs 49 mmHg, P < 0.05) but no change in heart rate. Acute hyperhomocysteinaemia had no significant effect on incremental microvascular vasodilator dose-response curves to Ach and SNP, or circulating levels of vWF.


CONCLUSIONS
The present study shows that acute hyperhomocysteinaemia increases pulse pressure (a marker of large vessel stiffness) but has no effect on endothelial-dependent (non-NO-mediated) microvascular vasodilation.
Davis
K R
KR
School of Medical and Surgical Sciences, University of Nottingham, UK.
Pearson
H
H
Moat
S
S
Bonham
J R
JR
Donnelly
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008715:Methionine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011312:Pressure; D011674:Pulse; D012867:Skin / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D006710:Homocysteine; D009599:Nitroprusside; D008715:Methionine; D000109:Acetylcholine