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 (L DL) but not high density lipoprotein (HDL) stimulated NO production at 12, 24 and 48 hr of incubation with macrophages. Forty-eight hour inc ubation of macrophages with VLDL or LDL increased NO production from 1 0.8 nmoles/l0(6) cells in control to 249 and 60 nmoles/l0(6) cells,res pectively. VLDL-induced nitric oxide production was 825 nmoles/10(6) a fter 12 days of incubation. VLDL by itself or in the presence of LDL a nd HDL induced similar levels of NO in 24 hrs. Lipoproteins were witho ut effect on NO, when incubated with macrophages in the absence of L-a rginine and in the presence of nitric oxide synthase inhibitor monomet hyl-L-arginine (L-NMMA). Oxidized VLDL was as effective as native form in the induction of macrophage NO, whereas oxidized LDL did not induc e NO production. Further, the presence of 100 mu M vitamin E in the in cubation had no effect on VLDL- and LDL-induced NO production. Preincu bation of macrophages with VLDL and LDL for 3hr or 6hrs activated macr ophages to generate NO. These effects of lipoproteins could be of inte rest in the pathophysiology of lipoproteins and NO mediated diseases. (C) 1994 Academic Press, Inc.