Nitric oxide (NO) has a broad range of biological activities and has been implicated in signaling pathways in phylogenetically diverse species. Nitric oxide synthases (NOSs), the enzymes responsible for synthesis of NO, contain an N-terminal oxygenase domain and a C-terminal reductase domain. eNOS is a calcium/calmodulin dependent enzyme which undergoes several post translational modifications, including acylation with myristate and palmitate, and phosphorylation on numerous residues. As with the other members of the NOS family, eNOS derives the diffusible multifunctional second messenger NO from L arginine through a series of reactions in which L citrulline is an intermediate. eNOS plays an important role in controlling vascular tone, platelet aggregation, and cardiac myocyte function.