Nitric oxide synthase and vascular dysfunction in sepsis: Should we target nitric oxide synthase 1, nitric oxide synthase 2, both, or neither?

摘要

Together with carbon monoxide and hydrogen sulfide, nitric oxide (NO) is recognized as being one of three gaseous molecules that play important roles as signaling agents in mammalian biology. NO is generated in cells via a reaction that uses the amino acid L-arginine and molecular oxygen as substrates. This reaction is catalyzed by a family of enzymes called "nitric oxide synthases" (NOSs). Three NOS isoforms are known: NOS1 (neuronal NOS); NOS2 (inducible NOS); and NOS3 (endothelial NOS). The enzymatic activity of NOS1 and NOS3 is controlled by changes in intracellular calcium ion (Ca~(2+)) concentration. By contrast, the enzymatic activity of NOS2 is independent of Ca~(2+) concentration. NOS1 and NOS3 are expressed constitutively although the expression of these proteins can be up-regulated under certain conditions (1,2). NOS2 is an inducible protein and its expression in mac-rophages and other cell types can be triggered by various pro-inflammatory mediators.