[Metabolism and regulation of nitric oxide: a hard-to-control mediator]

Although nitric oxide (NO) is implicated in numerous regulatory mechanisms, its therapeutic use remains problematic. Synthesis of this mediator of low specificity with multiple effects involves two types of enzymes (constitutive and inducible). The complexity of the corresponding regulatory mechanisms precludes control for therapeutic use. As NO interacts with numerous metabolic pathways and can also be stored, interpretation of experimental results is difficult, which hinders development of therapeutic trials. In addition, NO is a free radical and thus participates in the free radical cascade. Another difficulty in use of NO is its role in equilibrium implicating still poorly understood mediators (such as endothelin at a vascular level). The complexity of NO pathways explains why therapeutic trials of NO to date have proven unsatisfactory except for treatment of arterial pulmonary hypertension.