The toxicology of inhaled nitric oxide

Inhaled nitric oxide is a targeted pulmonary vasodilator that improves clin ical outcomes for newborn patients with persistent pulmonary hypertension o f the newborn, and may be effective in treating some premature patients wit h acute respiratory distress syndrome or lung disease of prematurity. Nitri c oxide is now recognized as playing an important role in the regulation of diverse physiological processes. However, the pharmacological properties o f inhaled nitric oxide are not easy to separate from its toxicological effe cts. For example, the intended effect of inhaled nitric oxide, vasodilation in the lung, is mediated, in part, by increased cellular cyclic GMP (cGMP) . However, increased cGMP can also interfere with normal cellular prolifera tion. Nitric oxide has also been shown to cause DNA strand breaks and/or ba se alterations that are potentially mutagenic, Inhaled nitric oxide can rap idly react with oxygen in the lung to form nitrogen dioxide, which is a pot ent pulmonary irritant, Nitric oxide also reacts with superoxide anion to f orm peroxynitrite, a cytotoxic oxidant that can interfere with surfactant f unctioning. The overall effect of inhaled nitric oxide in potentiating or a ttenuating inflammation and oxidative damage in diseased lung is dependent on the dose administered, Furthermore, despite rapid inactivation by circul ating hemoglobin, inhaled nitric oxide exerts effects outside the lung, inc luding blocking platelet aggregation, causing methemoglobinemia, and possib ly inducing extrapulmonary vasodilation. The toxicology of inhaled nitric o xide is not completely understood and must be considered in the design of p rotocols for its safe and effective clinical use.