The effect on endothelial function of vitamin C during methionine induced hyperhomocysteinaemia.
BACKGROUND
Manipulation of total homocysteine concentration with oral methionine is associated with impairment of endothelial-dependent vasodilation. This may be caused by increased oxidative stress. Vitamin C is an aqueous phase antioxidant vitamin and free radical scavenger. We hypothesised that if the impairment of endothelial function related to experimental hyperhomocysteinaemia was free radically mediated then co-administration of vitamin C should prevent this.


METHODS
Ten healthy adults took part in this crossover study. Endothelial function was determined by measuring forearm blood flow (FBF) in response to intra-arterial infusion of acetylcholine (endothelial-dependent) and sodium nitroprusside (endothelial-independent). Subjects received methionine (100 mg/Kg) plus placebo tablets, methionine plus vitamin C (2 g orally) or placebo drink plus placebo tablets. Study drugs were administered at 9 am on each study date, a minimum of two weeks passed between each study. Homocysteine (tHcy) concentration was determined at baseline and after 4 hours. Endothelial function was determined at 4 hours. Responses to the vasoactive substances are expressed as the area under the curve of change in FBF from baseline. Data are mean plus 95% Confidence Intervals.


RESULTS
Following oral methionine tHcy concentration increased significantly versus placebo. At this time endothelial-dependent responses were significantly reduced compared to placebo (31.2 units [22.1-40.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo). Endothelial-independent responses were unchanged. Co-administration of vitamin C did not alter the increase in homocysteine or prevent the impairment of endothelial-dependent responses (31.4 [19.5-43.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo)


CONCLUSIONS
This study demonstrates that methionine increased tHcy with impairment of the endothelial-dependent vasomotor responses. Administration of vitamin C did not prevent this impairment and our results do not support the hypothesis that the endothelial impairment is mediated by adverse oxidative stress.
Hanratty
C G
CG
Dept of Therapeutics and Pharmacology, The Queen's University of Belfast, UK. cghanratty@hotmail.com
McGrath
L T
LT
McAuley
D F
DF
Young
I S
IS
Johnston
D G
DG
D000109:Acetylcholine / Q000008:administration & dosage; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D007269:Injections, Intra-Arterial; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D010991:Plethysmography; D012039:Regional Blood Flow; D016037:Single-Blind Method; D014664:Vasodilation / Q000502:physiology
D006710:Homocysteine; D008715:Methionine; D000109:Acetylcholine; D001205:Ascorbic Acid