Oxidized low-density lipoprotein decreases the induced nitric oxide synthesis in rat mesangial cells

Recently, the close relation between oxidized low density lipoprotein (Ox-LDL) and the progression of glomerular injury has been demonstrated. The nitric oxide (NO) pathway in glomerular mesangial cells may be a potential target for the adverse effects of Ox-LDL in the development of glomerular injury. In this study, we treated cultured rat mesangial cells (RMC) with Fe(2+)-oxidized LDL and then stimulated the cells with lipopolysacharride (LPS, 10 micrograms ml-1). The LPS-induced NO production, assessed by NO2-concentrations in cultured supernatants, decreased from 7.83 nmol per 10(6) cells in control to 4.00 nmol per 10(6) cells and 1.67 nmol per 10(6) cells in RMC preincubated with Ox-LDL at 20 micrograms ml-1 and 40 micrograms ml-1, respectively (P < 0.01). Native LDL had no significant effects on LPS-induced NO production. Using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we could not detect significant alteration of inducible NO synthase (iNOS) mRNA levels in RMC preincubated with Ox-LDL. Our results suggest that Ox-LDL decreases induced NO production in RMC, which may contribute to the adverse effects of Ox-LDL in progressive glomerular injury. The mechanisms of this decrease may not involve changes of iNOS genic transcription.