Inhibition of constitutive and inducible nitric oxide synthase: potential selective inhibition

Nitric oxide (NO) is a molecule that has been shown to be involved in a diverse array of physiological events. A variety of disease states and disorders are, in fact, due to either an over- or an underproduction of NO. As a result of the ubiquity and diversity of NO-mediated phenomenon, pharmacological manipulation is difficult. NO biosynthesis is the result of an oxidation of a terminal nitrogen on the amino acid arginine by a class of enzymes generally referred to as the nitric oxide synthases (NOSs). Since the various isoforms of NOS are distributed in cells and tissues according to their function, there is the possibility that manipulation of NO levels can be accomplished by designing specific pharmacological agents targeted at a single NOS isoform. Thus, this review discusses general inhibition of the NOSs by a variety of agents and then focuses on the possibility of developing agents for specific isoform inhibition.