Effects Of Ox-LDL On INOS Gene Expression And NO Production In Rat Vascular Smooth Muscle Cells And Study On Antioxidation Of α-Lipoic Acid

Background: Nitric oxide is one of the most effective vasodilators invivo. It can inhibit several atherogenic processes such as VSMC proliferation, platelet aggregation, monocyte adhesion and even oxidative modification, ox-LDL plays an important role in many stages of AS. Recently, it is reported that ox-LDL can impaire the endothelium dependent vasodilation. So, the atherogenic effects of ox-LDL may be mediated, in part, by it's effects on NO.Objective: To investigate the influence of ox-LDL and antioxidant LAon iNOS gene expression and NO production in cultured rat aortic VSMC activated with IL-1 3 ; The effect of LA on the oxidative modification of LDL induced by Cu2+ is also abserved.Methods: The level of iNOS gene expression was detected by SQ-RT-PCR. NO production was estimated by using NO kits to measure nitrite accumulation-one of NO's stable breakdown products in the media. The extant of lipid peroxidation was measured by TEARS test.Results: 1. ox-LDL significantly decreased iNOS gene expression andattenuated NO production (PO.01), whereas, native LDL had no effect on them (P>0.05); The inhibitory effect of ox-LDL was associated with it's concentration and degree of oxidative modification(P<0.01, PO.05). 2. When ox-LDL was pretreated with LA, the iNOS gene expression and NO production were elavated compared with ox-LDL group (P<0.01). 3. LA inhibited the formation of TBARS in a dose dependent manner (P<0.01).Conclusion: 1.Oxidized but not native LDL decreases iNOS geneexpression and NO production. The inhibitory effect is dose dependent and is associated with it's degree of oxidative modification. 2. LA can release the inhibitory effect of ox-LDL on iNOSmRNA and NO production levels. 3. LA inhibits the oxidative modification of LDL induced by Cu2+ in vitro in a dose dependent manner.