Nitric oxide (NO) is a potent bio-regulatory molecule, which plays important roles in the regulation of a variety of normal developmental and physiological processes. NO is generated by nitric oxide synthase (NOS) in a reaction which converts L-arginine and oxygen into citrulline and nitric oxide. Three distinct mammalian genes have been identified which encode NOS isoforms: neuronal (nNOS or bNOS), macrophage or inducible (iNOS), and endothelial (eNOS). The NOS isoforms can be subdivided into two general categories, constitutive or inducible, based on differences in their regulation and activities. The constitutive isoforms include eNOS and nNOS.These isoforms are always present but remain inactive until an increase in intracellular calcium results in enhanced calcium/calmodulin binding and subsequent activation. In contrast, the inducible NOS isoform, iNOS, is not normally expressed, but is induced (though alterations in gene expression, mRNA stability, or protein synthesis) in response to certain cytokines.