L-arginine supplementation improves venous endothelial cell but not smooth muscle cell dysfunction induced by prolonged diet-induced hypercholesterolemia

Hypercholesterolemia induces venous vasomotor dysfunction. This study examines the endothelial and smooth muscle cell vasoreactivity of external jugular veins from rabbits fed either a normal or a 1% cholesterol diet for 8 weeks with and without L-arginine supplementation (2g/kg day^-1 orally for the last 5 weeks). Isometric tension studies were performed on harvested jugular veins. Concentrations of serum cholesterol were 20-fold higher than controls and serum L-arginine twofold higher than untreated animals. Hypercholesterolemia induced hypersensitivity to norepinephrine (p < .05), bradykinin (p < .05), and histamine (p < .05) with a contractile response to serotonin compared to controls. L-Arginine supplementation decreased bradykinin hypersensitivity but had no effect on the changes in norepinephrine serotonin and histamine responses compared to controls. Hypercholesterolemia interfered with relaxation induced by acetylcholine but with L-arginine, normal acetylcholine-induced, endothelium-dependent relaxation returned (54 ± 10%, compared to 40 ± 14% in control veins; p >.05). Non-endothelium-dependent relaxation to sodium nitroprus-side of precontracted veins was unaffected by the presence of high cholesterol concentrations. This study suggests that L-arginine therapy may ameliorate hypercholesterolemia-induced functional abnormalities in endothelial cells.