Localization and regulation of nitric oxide synthase isoforms in the kidney

Nitric oxide synthases (NOS), which comprise a multi-gene family, play important roles in a variety of physiological and pathophysiological processes in the kidney. The three major NOS isoforms are expressed in a cell type--specific manner and are subject to complex and distinct control mechanisms. Although knowledge about the intrarenal distribution and regulation of the major NOS isoforms has been expanding, recent advances in the molecular details of the structure, function, and regulation of the NOS genes and the enzymes they encode have added considerable complexity to the effort. Molecular biological studies have identified alternative splice variants of NOS1 and NOS2 that appear to be subject to unique regulation and may encode functionally distinct proteins. The renal distribution of these new variants has yet to be explored in detail. In addition, newly discovered transcriptional and posttranscriptional control mechanisms, including alternative promoter usage, protein-protein interactions, and phosphorylation events, for the three major NOS isoforms await characterization in renal cells. This review highlights the current state of knowledge about the distribution and regulation of the NOS isoforms in the kidney, and identifies new opportunities for further renal investigation.