Regulation of inducible nitric oxide synthase expression in rat mesangial cells and isolated glomeruli

Kidney International
M SauraS Lamas

Abstract

The presence of the inducible isoform of nitric oxide synthase (iNOS) in glomerular mesangial cells facilitates the synthesis of nitric oxide (NO) after stimulation with cytokines or lipopolysaccharide (LPS). As the role of NO within the glomerulus may be important in conditions such as glomerulonephritis, we have studied the effect of dexamethasone (DX) and pirrolidine dithiocarbamate (PDTC), an inhibitor of the nuclear transcription factor, NF-kappa B activation on the induced synthesis of NO in rat mesangial cells (RMC). LPS, tumor necrosis factor-alpha (TNF-alpha) and the combination of both were able to induce NO synthesis in a dose-dependent manner as measured with the determination of NO2- levels. Treatment with LPS (10 micrograms/ml) + TNF-alpha (100 ng/ml) for eight hours was the most potent stimulus for iNOS activity. DX (1 microM) had an inhibitory effect on LPS-, TNF-alpha- and LPS + TNF-alpha-induced NO synthesis (51.2, 42.5 and 68% of inhibition, respectively). The inhibitory effect of DX was confirmed using a reporter cell bioassay, whereas cGMP was measured as a reflection of bioactive NO. DX inhibited induced NO synthesis when RMC were exposed to this agent before (16 hr of pretreatment, 75.7% inhibition) or at...Continue Reading

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