Acute hyperhomocysteinemia induces a reduction in arterial distensibility and compliance.
OBJECTIVE
The aim of the study was to evaluate the effects of acute hyperhomocysteinemia on distensibility and compliance of large peripheral arteries. Isoprostanes generation and antioxidant vitamins were used to assess the role of oxidative stress.


METHODS
A cross-over, double-blind study on distensibility (DC: distensibility coefficient) and compliance (CC: cross-sectional compliance) of common femoral and brachial arteries was performed in 12 healthy young male volunteers by means of a wall track system before and 4 h after a single oral methionine (100 mg/kg) or placebo administration. The effects of methionine load were investigated also after oral administration of vitamin C (1g/day) and vitamin E (800 mg/day) for 8 consecutive days.


RESULTS
Oral methionine induced a significant increase in plasmatic levels of homocysteine. Distensibility and compliance of brachial and femoral arteries were significantly reduced after methionine load in comparison to placebo. This acute impairment of arterial wall mechanical properties was associated to endothelial dysfunction, since altered flow-dependent vasodilatation (P < 0.05 versus placebo) was observed in the same arterial districts. A significant increase in urinary 8-iso-prostaglandin F2alpha was observed after methionine. Pretreatment with vitamins C and E prevented the effects of methionine on femoral and brachial arteries as well as on urinary 8-iso-prostaglandin F2alpha excretion.


CONCLUSIONS
Hyperhomocysteinemia seems responsible for altered arterial wall elasticity and for endothelial dysfunction. A pivotal role can be attributed to oxidative stress.
Arcaro
Guido
G
Departments of Medical and Surgical Sciences, University of Verona, Italy. guido.arcaro@tiscali.it
Fava
Cristiano
C
Dagradi
Roberta
R
Faccini
Giovanni
G
Gaino
Stefania
S
Degan
Maurizio
M
Lechi
Clara
C
Lechi
Alessandro
A
Minuz
Pietro
P
D000208:Acute Disease; D000328:Adult; D001205:Ascorbic Acid / Q000627:therapeutic use; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects* / Q000503:physiopathology; D003187:Compliance / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005263:Femoral Artery / Q000187:drug effects* / Q000503:physiopathology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D012039:Regional Blood Flow; D013997:Time Factors; D014664:Vasodilation
D006710:Homocysteine; D008715:Methionine; D001205:Ascorbic Acid