The role of endogenous and exogenous nitric oxide on airway function.

Coordinated regulation of airway caliber is important for the maintenance of effective ventilation. Therefore, we sought to characterize the role of endogenously released, and exogenously administered, nitric oxide (NO) in mediating airway smooth muscle relaxation during early postnatal life. In both rat pup and piglet models, cholinergically mediated airway contractile responses were diminished by simultaneous release of endogenous NO and cGMP activation in both central airways and peripheral contractile elements. This ability of endogenously released NO to oppose airway constriction may be impaired in response to hyperoxic exposure or in animal models of cystic fibrosis. Additional studies in piglets have shown that exogenously administered NO causes a modest, but significant, reduction in lung resistance, analogous to the decrease in pulmonary vascular resistance induced by inhaled NO. Clinical trials are now underway in preterm infants at risk for chronic neonatal lung injury to determine whether inhaled NO has a beneficial effect on the development of bronchopulmonary dysplasia and whether exogenous NO modulates airway function in such infants.