Very low density and low density lipoproteins induce nitric oxide synthesis in macrophages

The effect of lipoproteins on rat peritoneal macrophage nitric oxide (NO) production was studied. Very low density (VLDL) and low density (LDL) but not high density lipoprotein (HDL) stimulated NO production at 12, 24 and 48 hr of incubation with macrophages. Forty-eight hour incubation of macrophages with VLDL or LDL increased NO production from 10.8 nmoles/10(6) cells in control to 249 and 60 nmoles/10(6) cells, respectively. VLDL-induced nitric oxide production was 825 nmoles/10(6) after 12 days of incubation. VLDL by itself or in the presence of LDL and HDL induced similar levels of NO in 24 hrs. Lipoproteins were without effect on NO, when incubated with macrophages in the absence of L-arginine and in the presence of nitric oxide synthase inhibitor monomethyl-L-arginine (L-NMMA). Oxidized VLDL was as effective as native form in the induction of macrophage NO, whereas oxidized LDL did not induce NO production. Further, the presence of 100 microM vitamin E in the incubation had no effect on VLDL- and LDL-induced NO production. Preincubation of macrophages with VLDL and LDL for 3hr or 6hrs activated macrophages to generate NO. These effects of lipoproteins could be of interest in the pathophysiology of lipoproteins and NO mediated diseases.