AIMS: 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.
RCT Entities:
AIMS: 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.
Authors: I M Graham; L E Daly; H M Refsum; K Robinson; L E Brattström; P M Ueland; R J Palma-Reis; G H Boers; R G Sheahan; B Israelsson; C S Uiterwaal; R Meleady; D McMaster; P Verhoef; J Witteman; P Rubba; H Bellet; J C Wautrecht; H W de Valk; A C Sales Lúis; F M Parrot-Rouland; K S Tan; I Higgins; D Garcon; G Andria Journal: JAMA Date: 1997-06-11 Impact factor: 56.272
Authors: J Selhub; P F Jacques; A G Bostom; R B D'Agostino; P W Wilson; A J Belanger; D H O'Leary; P A Wolf; E J Schaefer; I H Rosenberg Journal: N Engl J Med Date: 1995-02-02 Impact factor: 91.245
Authors: M den Heijer; T Koster; H J Blom; G M Bos; E Briet; P H Reitsma; J P Vandenbroucke; F R Rosendaal Journal: N Engl J Med Date: 1996-03-21 Impact factor: 91.245
Authors: G Vyssoulis; E Karpanou; S-M Kyvelou; D Adamopoulos; T Gialernios; E Gymnopoulou; D Cokkinos; C Stefanadis Journal: J Hum Hypertens Date: 2009-06-11 Impact factor: 3.012