L-arginine supplementation improves venous endothelial cell but not smooth muscle cell dysfunction induced by...

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 (2 g/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 nitroprusside 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.