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 (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.
Davies
M G
MG
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Barber
E
E
Dalen
H
H
Hagen
P O
PO
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D001920:Bradykinin / Q000494:pharmacology; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000503:physiopathology*; D007601:Jugular Veins / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D011189:Potassium Chloride; D006632:Histamine; D001120:Arginine; D001920:Bradykinin; D009638:Norepinephrine