Abstract 1798 Pulmonary: Reactive Airway Diseases I Poster Symposium, Monday, 5/3

In the present studies we sought to define the effect of maturation and hyperoxic stress on nitric oxide (NO)-induced modulation of bronchopulmonary responses to vagal stimulation. Experiments were performed on decerebrate, paralyzed and ventilated rat pups of 6-7 (n=22) and 13-15 days of age (n=23) breathing room air, and on rat pups of 13-15 days of age (n=19) following exposure to hyperoxia (≥95% FiO2 for 4-6 days). Total lung resistance (RL) was measured by body plethysmograph, and calculated using ANADAT 5.2 software. Vagal stimulation caused a frequency dependent increase in RL in normoxic animals at both ages. The response to vagal stimulation was significantly potentiated by prior blockade of nitric oxide synthase (L-NAME, 30 µg/g; p<0.05), an enzyme which is required for NO generation. As expected, exposure to hyperoxic stress increased contractile responses to vagal stimulation (p<0.05). However, after hyperoxic exposure the potentiation of contractile responses by prior blockade of NOS activity was abolished. We conclude that NO plays an important role in modulating bronchopulmonary contractile responses to endogenously released acetylcholine in rats during development. Loss of this modulatory effect of NO by hyperoxia could contribute to bronchopulmonary hyperresponsiveness observed after prolonged exposure to hyperoxic stress.

Supported by NIH HL grants 50527 and 56470.