Inhibition of endothelial nitric oxide generation by low-density lipoprotein is partially prevented by L-arginine and L-ascorbate.
We evaluated, in endothelial cells, the relative effectiveness of L-arginine and L-ascorbate in preventing the decrease in nitric oxide (NO) production in response to native low-density lipoprotein (LDL) from healthy subjects (nLDL), oxidized LDL (oxLDL, formed by nLDL oxidation) or native LDL from type 2 diabetic patients (dLDL). Human umbilical vein endothelial cells (HUVEC) were exposed to nLDL, dLDL or oxLDL (100 mg protein/L), in the absence or presence of L-arginine 10(-4)mol/L and/or L-ascorbate 10(-4)mol/L; NO synthase (NOS) activity and cyclic guanosine-3',5'-monophosphate (cGMP) were measured by the conversion of L-[3H]-arginine to L-[3H]citrulline and by radioimmunoassay, respectively. Both L-arginine and L-ascorbate increased cGMP in HUVEC co-incubated with any LDL species, although to lower levels than found in the absence of LDL. L-ascorbate did not affect NOS activity, whereas L-arginine increased it, both in the absence and presence of all LDL species. The effects of combined L-arginine and L-ascorbate on NOS activity and cGMP were no greater than those of L-arginine alone. Our results suggest that L-arginine or L-ascorbate can ameliorate, but not normalize, NO production in this situation, and that combining L-arginine with L-ascorbate is unlikely to produce additional benefit as compared with L-arginine alone.
Ji
Yong
Y
Atherosclerosis Research Centre, Nanjing Medical University, Nanjing 210029, PR China.
Han
Yi
Y
Diao
Jianxin
J
Huang
Yan
Y
Chen
Qi
Q
Ferro
Albert
A
D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D042783:Endothelial Cells; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*
D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D001205:Ascorbic Acid