Lack of effect of vitamin E on L-arginine-responsive endothelial dysfunction in patients with mild hypercholesterolaemia and coronary artery disease.
1. Dietary supplementation with vitamin E reduces ischaemic events in patients with established coronary artery disease and improves endothelial function in cholesterol-fed rabbits. We examined whether such dietary supplementation with vitamin E improves endothelial function in patients with mild hypercholesterolaemia and coronary artery disease. 2. Twenty patients (total cholesterol 6.8 +/- 1.1 mmol/l, mean +/- SD) with angiographically documented coronary artery disease were randomly allocated to receive placebo (n = 10) or vitamin E, 400 i.u. daily, (n = 10) for 8 weeks. Endothelium-dependent and independent vasodilatation within forearm vasculature was assessed by brachial artery infusion of acetylcholine (co-infused with saline vehicle and L-arginine) and nitroprusside before and after supplementation. 3. Plasma concentrations of vitamin E increased from 32.9 +/- 3.8 to 69.1 +/- 11.8 mumol/l (means +/- SE) in the vitamin E-supplemented group (P < 0.01) but did not change significantly in the placebo group. Lipid profiles remained similar before and after supplementation in both groups. Forearm blood flow responses to acetylcholine (7.5 and 15 micrograms/min) and nitroprusside (3 and 10 micrograms/min) were similar before and after supplementation in both groups. Acute intra-arterial administration of L-arginine (10 mg/min) augmented the response to acetylcholine (15 micrograms/min) in both groups before and after supplementation to a similar degree (mean augmentation: 60 +/- 18%, P < 0.01). 4. Acute administration of L-arginine reverses endothelial dysfunction in forearm vasculature of patients with mild hypercholesterolaemia and coronary artery disease but supplementation with vitamin E (400 i.u. daily) for 8 weeks does not reverse L-arginine-responsive endothelial dysfunction.
Chowienczyk
P J
PJ
Department of Clinical Pharmacology, UMDS, St Thomas' Hospital, London, U.K.
Kneale
B J
BJ
Brett
S E
SE
Paganga
G
G
Jenkins
B S
BS
Ritter
J M
JM
D000109:Acetylcholine; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001120:Arginine / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents; D014810:Vitamin E / Q000008:administration & dosage*
D014665:Vasodilator Agents; D014810:Vitamin E; D009599:Nitroprusside; D001120:Arginine; D000109:Acetylcholine