Acute hyperhomocysteinaemia affects pulse pressure but not microvascular vasodilator function

Aims Raised homocysteine (hcy) levels are associated with premature coronar y artery disease, but the underlying vascular mechanism and the extent to w hich 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 (t o induce acute hyperhomocysteinaemia) on cutaneous microvascular vasodilato r responses to incremental-dose iontophoretic administration of acetylcholi ne (Ach) and sodium nitroprusside (SNP) using laser Doppler fluximetry (LDF ), and the effects on von Willibrand factor (vWF) levels and systemic haemo dynamics. Results Methionine administration produced a three fold rise in plasma hcy levels at 8 h, which was accompanied by a significant increase in pulse pre ssure (53 vs 49 mmHg, P < 0.05) but no change in heart rate. Acute hyperhom ocysteinaemia had no significant effect on incremental microvascular vasodi lator dose-response curves to Ach and SNP, or circulating levels of vWF. Conclusions The present study shows that acute hyperhomocysteinaemia increa ses pulse pressure (a marker of large vessel stiffness) but has no effect o n endothelial-dependent (non-NO-mediated) microvascular vasodilation.