Nitric oxide, the biological mediator of the decade: fact or fiction?

Nitric oxide (NO), an atmospheric gas and free radical, is also an important biological mediator in animals and humans. Its enzymatic synthesis by constitutive (c) and inducible (i) isoforms of NO synthase (NOS) and its reactions with other biological molecules such as reactive oxygen species are well characterized. NO modulates pulmonary and systemic vascular tone through its vasodilator property. It has antithrombotic functions and mediates some consequences of the innate and acute inflammatory responses; cytokines and bacterial toxins induce widespread expression of iNOS associated with microvascular and haemodynamic changes in sepsis. Within the lungs, a diminution of NO production is implicated in pathological states associated with pulmonary hypertension, such as acute respiratory distress syndrome: inhaled NO is a selective pulmonary vasodilator and can improve ventilation-perfusion mismatch. However, it may have deleterious effects through modulating hypoxic pulmonary vasoconstriction. Inhibitors of NOS may be of benefit in inotrope-refractory septic shock, but toxicity of newly developed selective iNOS inhibitors have prevented clinical trials of efficacy. An expanding literature on the origins and measurement of NO in exhaled breath implicates NO as a potentially useful marker of disease activity in respiratory tract inflammation in the future. This report reviews some aspects of research into the clinical importance of nitric oxide.