Hyperoxic exposure causes inflammatory changes in the newborn lung that contribute to neonatal pulmonary injury. Despite recent reports that NO is involved in airway inflammation, the role of endogenous NO production during oxygen induced lung injury remains controversial. We hypothesized that the inflammation induced by hyperoxia would increase inducible Nitric Oxide Synthase (iNOS) expression and NO activity in the young rat. Twenty-eight 3 week-old Sprague-Dawley rats were separated into 2 groups of 14 and exposed to either normoxia or 100% O2 for 7 days. Seven rats in each group received the iNOS inhibitor Aminoguanindine (AG) at 400 mg/kg/d. After 7 days, rat lungs were analyzed for iNOS mRNA production by Northern blot, and cGMP levels by radioimmunoassay to assess NO activity. Hyperoxia produced a two-fold increase in iNOS mRNA and significantly increased cGMP vs. normoxic controls (fig). AG attenuated but did not abolish the hyperoxia-induced increase in cGMP, suggesting a contribution from other NOS isoforms. We conclude that iNOS expression in the lung is stimulated during hyperoxia, leading to an increase in NO activity. We speculate that iNOS regulation and NO production play an important role in mediating the inflammatory responses that contribute to neonatal lung injury. Supp by HL 25803 and 50527.

figure 1

Figure 1