Role of endogenous nitric oxide in hyperoxia-induced airway hyperreactivity in maturing rats

We sought to define the effects of maturation and hyperoxic stress on nitri c oxide (NO)-induced modulation of bronchopulmonary responses to stimulatio n of vagal preganglionic nerve fibers. Experiments were performed on decere brate, paralyzed, and ventilated rat pups at 6-7 days (n = 21) and 13-15 da ys of age (n = 23) breathing room air and on rat pups 13-15 days of age (n = 19) after exposure to hyperoxia (greater than or equal to 95% inspired O- 2 fraction for 4-6 days). Total lung resistance (RL) and lung elastance (EL ) Were measured by body plethysmograph. Vagal stimulation and release of ac etylcholine caused a frequency-dependent increase in RL and EL in all anima ls. The RL response was significantly potentiated in normoxic animals by pr ior blockade of nitric oxide synthase (NOS) (P < 0.05). Hyperoxic exposure increased responses of RL to vagal stimulation (P < 0.05); however, after h yperoxic exposure, the potentiation of contractile responses by NOS blockad e was abolished. The response of EL was potentiated by NOS blockade in the 13- to 15-day-old animals after both normoxic and hyperoxic exposure (P < 0 .01). Morphometry revealed no effect of hyperoxic exposure on airway smooth muscle thickness. We conclude that NO released by stimulation of vagal pre ganglionic fibers modulates bronchopulmonary contractile responses to endog enously released acetylcholine in rat pups. Loss of this modulatory effect of NO could contribute to airway hyperreactivity after prolonged hyperoxic exposure, as may occur in bronchopulmonary dysplasia.