Nitric oxide and glomerulonephritis.

The glomerulus is a unique vascular network with the potential to express several isoforms of nitric oxide synthase (NOS). Induction of inducible NOS (iNOS) occurs as part of a rapid initial response to immune injury in glomerulonephritis (GN). Studies on rodent models suggest that this is due to activation of transcription factors by reactive oxygen species (ROS), generated in responses to Fcgamma and CR engagement. iNOS operates in a complex milieu among multiple other inflammatory mediators, changing expression of constitutive NOS (endothelial NOS, eNOS), a critical regulator of glomerular function, and auto-regulating its own expression. As yet there is no consensus as to the role of high output NO generated by iNOS in the glomerulus, although many studies have demonstrated that NO inhibition can alter the level of proteinuria and leukocyte infiltration, and other manifestations of injury such as thrombosis, proliferation, and matrix production. This article reviews the evidence accumulated from experimental studies over the past decade, and discusses how these conflicting data can be reconciled to form a working hypothesis on the role of NO in GN.