INHIBITORY EFFECT OF INDUCIBLE TYPE NITRIC-OXIDE SYNTHASE ON OXIDATIVE MODIFICATION OF LOW-DENSITY-LIPOPROTEIN BY VASCULAR SMOOTH-MUSCLE CELLS

Oxidative modification of low density lipoprotein (LDL) plays an impor tant role in atherogenesis. Inducible type nitric oxide synthase (iNOS ) has been shown to be expressed in vascular smooth muscle cells (VSMC ) of atherosclerotic arteries. Nitric oxide (NO) donors have been show n to inhibit metal ion-or cell-mediated oxidation of LDL. To elucidate whether NO produced by iNOS in VSMC inhibit oxidation of LDL, we inve stigated the effect of NO donors and iNOS-induction in VSMC on oxidati on of LDL. NO donor, S-Nitroso-n-acetylpenicillamine (SNAP) or 3-morph olinosydnonimine (SIN-1) (0.1-1.0 mmol/l) dose-dependently reduced cop per-induced oxidation of LDL as demonstrated by the inhibition of elec trophoretic mobilities on agarose gels and the formation of thiobarbit uric acid-reactive substances (TEARS) and conjugated dienes. Moreover, treatment with IL-1 beta (5-50 ng/ml) reduced the increases in electr ophoretic mobilities on agarose gels and TEARS formation in associatio n with increases in NO production. In addition, inhibition of NO produ ction by N-G-monomethyl-L-arginine monoacetate reduced the inhibitory effect of IL-1 beta on LDL oxidation. These results indicate that NO r elease via iNOS action induced by cytokines in VSMC may play protectiv e roles in oxidative modification of LDL during the atherosclerosis pr ocess. (C) 1998 Elsevier Science Ireland Ltd.