Effect Of Anti-Oxidant Treatment And Cholesterol Lowering On Resting Arterial Tone, Metabolic Vasodilation And Endothelial Function In The Human Forearm: A Randomized, Placebo-Controlled Study

• Published in: Clinical and experimental pharmacology & physiology 2001-05, Vol.28 (5-6), p.409-418
• Main Authors: Duffy, Stephen J, O'Brien, Richard C, New, Gishel, Harper, Richard W, Meredith, Ian T
• Format: Article
• Language: English
• Subjects: Adult; anti-oxidants; Anticholesteremic Agents - pharmacology; Antioxidants - pharmacology; Blood Volume - drug effects; endothelial function; Endothelium, Vascular - drug effects; Exercise - physiology; Forearm - blood supply; Hemodynamics - drug effects; Humans; hypercholesterolaemia; lipid-lowering; Lipids - blood; Male; metabolic vasodilation; Muscle Tonus - drug effects; Muscle, Smooth, Vascular - drug effects; oxidative stress; Regional Blood Flow - drug effects; Vasodilation - physiology
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1046/j.1440-1681.2001.03458.x

SUMMARY 1. The aim of the present study was to determine whether anti‐oxidant therapy with vitamin E and/or cholesterol‐lowering therapy with simvastatin would augment resting forearm blood flow (FBF) and metabolic vasodilation in response to exercise and improve endothelial function in young patients with hypercholesterolaemia. 2. Endothelium‐dependent and ‐independent, nitric oxide (NO)‐mediated vasodilation have been shown to be impaired in young, otherwise healthy subjects with hypercholesterolaemia. Recent experimental and clinical studies suggest that vascular function may be improved with anti‐oxidant or cholesterol‐ lowering therapy, although these treatments may be synergistic. 3. We compared FBF at rest, in response to isotonic exercise, the endothelium‐dependent vasodilator acetylcholine (ACh), the endothelium‐independent vasodilator sodium nitroprusside (SNP) and the NO synthase inhibitor NG‐monomethyl‐L‐arginine (L‐NMMA) in 26 young, otherwise healthy volunteers (mean (±SD) age 29±7 years; 14 female, 12 male) with hypercholesterolaemia, before and after 6 months treatment with vitamin E, simvastatin and/or placebo. Treatment was randomized, double‐blinded in a 2 × 2 factorial design. Forearm blood flow was measured using venous occlusion plethysmography. 4. Vitamin E therapy increased plasma α‐tocopherol from 39.5±9.6 to 75.7±33.8 μmol/L (P < 0.001). Simvastatin reduced total cholesterol from 6.9±1.7 to 4.9±0.8 mmol/L and low‐ density lipoprotein (LDL) from 4.8±1.7 to 3.0±0.7 mmol/L (both P < 0.001), although total and LDL–cholesterol also decreased slightly in the placebo group. Vitamin E increased resting FBF from 2.1±0.3 to 2.4±0.3 mL/100 mL per min (P = 0.04) and decreased resting forearm vascular resistance from 42.1±4.2 to 36.1±3.4 units (P = 0.01), but the reduction in resting FBF with L‐NMMA was not affected. Vasodilation in response to isotonic exercise, ACh and SNP was similar before and after treatment in the placebo, vitamin E, simvastatin and in the combined vitamin E–simvastatin groups. NG‐Monomethyl‐L‐arginine infusion reduced resting FBF and functional hyperaemia in response to exercise and these responses were not altered by treatment. 5. These data suggest that while vitamin E therapy augments resting FBF and reduces forearm vascular resistance in young hypercholesterolaemic subjects, these effects may not be via NO‐dependent pathways. Metabolic vasodilation and responses to the NO‐mediated vasodilators ACh and SNP were not f