Nitric oxide (NO) is an unorthodox messenger molecule, which has numerous molecular targets. NO controls servoregulatory functions such as neurotransmission or vascular tone (by stimulating NO-sensitive guanylyl cyclase), regulates gene transcription and mRNA translation (e.g. by binding to iron-responsive elements), and produces post-translational modifications of proteins (e.g. by ADP ribosylation). In mammals, NO can be generated by three different isoforms of the enzyme NO synthase (NOS; l-arginine, NADPH:oxygen oxidoreductases, NO forming; EC The isozymes are referred to as neuronal ‘n’NOS (or NOS I), inducible ‘i’NOS (or NOS II), and endothelial ‘e’NOS (or NOS III).  The known NOS enzymes are usually referred to as ‘dimeric’ in their active form, ignoring the required calmodulins (CaMs) which, strictly speaking, mean they are tetramers (of two NOS monomers associated with two CaMs). They contain relatively tightly-bound cofactors (6R)-5,6,7,8-tetrahydrobiopterin (BH% ), FAD, FMN and iron protoporphyrin IX (haem) and probably (although see below) catalyse a reaction of arginine, NADPH, and oxygen to the free radical NO, citrulline and NADP. 
All isoforms of NOS utilize l-arginine as the substrate, and molecular oxygen and reduced nicotinamide-adenine-dinucleotide phosphate (NADPH) as co-substrates. All three NOS isozymes have regulatory functions in the cardiovascular system. Neuronal NOS is involved in central regulation of blood pressure, and nNOS-containing (nitrergic) nerves can dilate certain vascular beds. The most important isoform is eNOS, which keeps blood vessels dilated, controls blood pressure, and has numerous other vasoprotective and anti-atherosclerotic effects. iNOS is constantly active and not regulated by intracellular Ca2+ concentrations.


1.Alderton WK, et al. Biochem J. 2001;357(Pt 3):593–615.
2.F?rstermann U,et al. Eur Heart J. 2012;33(7):829–837d.