Inhaled nitric oxide therapy in adults.

Nitric oxide was largely regarded as a toxic pollutant until 1987, when its biologic similarities to endothelium-derived relaxing factor were demonstrated.1 Subsequently, nitric oxide and endothelium-derived relaxing factor were considered a single entity, modulating vascular tone through the stimulated formation of cyclic guanosine 3',5'-monophosphate (Fig. 1).2 Endogenous nitric oxide is formed from the semiessential amino acid L-arginine by one of three (neural, inducible, and endothelial) isoforms of nitric oxide synthase. The physiologic role of endogenous nitric oxide was first shown when an infusion of an inhibitor of all forms of nitric oxide synthase in healthy volunteers led to systemic and pulmonary pressor responses.3 However, the role of nitric oxide in maintaining low pulmonary vascular resistance in healthy persons has since been challenged.4 Inhaled nitric oxide had a negligible effect on pulmonary blood flow in healthy humans,5 but when healthy persons were breathing 12 percent oxygen, it reversed the pulmonary hypertension that was induced without affecting systemic hemodynamics.6 In 1991, inhaled nitric oxide was shown to be a selective pulmonary vasodilator in patients with pulmonary hypertension,7 as well as in animals with pulmonary hypertension induced by drugs or hypoxia.8 Two years later, inhaled nitric oxide emerged as a potential therapy for the acute respiratory distress syndrome (ARDS), because it decreased pulmonary vascular resistance without affecting systemic blood pressure and improved oxygenation by redistributing pulmonary blood flow toward ventilated lung units in patients with this condition.9 Despite such promise, the potential therapeutic role of inhaled nitric oxide in adults remains uncertain; licensed indications are restricted to pediatric practice. Furthermore, recent changes in the marketing of inhaled nitric oxide have dramatically increased its cost, which has inevitably led to a need to justify continuing its administration to adults. This review will consider the biologic actions of inhaled nitric oxide, discuss clinical indications for its administration in adults, and assess possible future developments.