Biochemical aspects of nitric oxide

Nitric oxide (NO), a free radical molecule, produced by NO synthase in the body exerts a number ofpathophysiological actions due to its chemical reactivity. Low amounts of NO (nM) normally produced by constitutiveNOS play a critical role in different physiological events such as vasodilation and neurotransmission. Higher amounts ofNO (mM) locally and spatially produced by inducible NOS during inflammation act as double-edged sword exerting eitherbeneficial or detrimental effects. Recently, new vision on the biological role of NO has been proposed based on thepossible cross-talk between constitutive and inducible NOS. Accordingly, normally produced low amounts of NO may beinvolved in the regulation of NF-kB activation and successively the expression of inducible NOS. Under normalconditions NF-kB activation is suppressed by low amounts of NO. Under conditions in which massive amounts of NOproduced by inducible NOS act detrimentally, NO-elicited down-regulation of NF-kB activation is compromised due tothe drop in NO at the early phase of inflammation caused by inactivation of constitutive NOS. Any treatment whichcounterparts the drop in NO, therefore, may present a new approach either in preventing or in treating inflammatorydiseases.