CHANGES IN INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION IN EXPERIMENTALGLOMERULONEPHRITIS

We assessed changes in transcriptional activation of the inducible iso form of nitric oxide synthase (iNOS) in a model of macrophage dependen t proliferative glomerulonephritis in the rat resembling human forms o f rapidly progressive nephritis, By the use of a cDNA probe derived fr om rat glomerular RNA and an RNase protection assay, iNOS expression w as assessed at early and tate stages of the disease and was correlated with the extent of macrophage infiltration, Prominent INOS expression occurred in isolated glomeruli 24 hr after onset of immune injury whe n marked glomerular infiltration by macrophages also occurred, Treatme nt of animals with immune injury with the arachidonic acid cyclooxygen ase inhibitor, indomethacin, potentiated iNOS expression, iNOS express ion was short-lived; it was markedly reduced on Day 2 of injury and un detectable on Days 4 and 10, despite sustained infiltration of glomeru li by macrophages. These observations suggest that in glomerular immun e injury the enhanced expression of INOS is not sustainable possibly d ue to downregulatory factors generated in the course of injury.