Reduction of nitric oxide synthase activity in human neutrophils by oxidized low-density lipoproteins. Reversal of the effect of oxidized low-density lipoproteins by high-density lipoproteins and L-arginine.
Oxidized low-density lipoproteins (ox-LDL) inhibit vascular relaxation by decreasing the synthesis or rapid degradation of endothelium-derived relaxing factor (EDRF), now identified to be nitric oxide (NO). We examined the regulation of NO synthase activity in human neutrophils, which also generate NO, by lipoproteins. Isolated human neutrophils were incubated with native-LDL, ox-LDL (10-50 micrograms protein/mL), high-density lipoproteins (HDL, 100 micrograms protein/mL) or HDL+ox-LDL, and NO synthase activity was measured as conversion of [3H]L-arginine to [3H]L-citrulline. Ox-LDL, but not native-LDL or HDL, significantly decreased NO synthase activity in human neutrophils. This effect of ox-LDL was incubation time and concentration dependent. The incubation of cells with HDL or L-arginine diminished the effects of ox-LDL on NO synthase activity. Thus, ox-LDL decreases the activity of NO synthase enzyme, and this effect of ox-LDL can be modified by HDL and L-arginine.
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002784:Cholesterol / Q000032:analysis; D002956:Citrulline / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine; D010084:Oxidation-Reduction; D013997:Time Factors
D004791:Enzyme Inhibitors; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D019335:Nitroarginine; D002956:Citrulline; D001120:Arginine; D002784:Cholesterol; D019001:Nitric Oxide Synthase