Effects of hyperoxia on nitric oxide synthase expression, nitric oxide activity, and lung injury in rat pups

Although hyperoxic exposure is an important contributor to the development of bronchopulmonary dysplasia and nitric oxide (NO) has been implicated in the pulmonary response to oxygen, the role of NO in mediating chronic neona tal lung injury is unclear. Therefore, rat pups were exposed to normoxia or hyperoxia (>95% O-2) from d 21 to 29. After the rats were killed, their lu ngs were removed for analysis of nitric oxide synthase (NOS) expression, NO activity as measured by 3',5'-cyclic guanosine monophosphate (cGMP) assay, and lung pathology. Hyperoxia caused 5-fold and 2-fold increases in induci ble (i) NOS and endothelial (e) NOS levels, respectively. NO activity was a ssessed by measuring cGMP levels after normoxic or hyperoxic exposure in th e presence and absence of NOS blockade with either aminoguanidine (AG) or N -omega-nitro-L-arginine (L-NNA). cGMP levels were elevated in hyperoxic ver sus normoxic rats (287 +/- 15 versus 106 +/- 9 pmol/mg protein, respectivel y, p < 0.001), and this increase in cGMP was attenuated after NOS blockade with either AG or L-NNA. Hyperoxic exposure significantly increased lung/bo dy weight ratios and induced histologic changes of interstitial and alveola r edema; however, these hyperoxia-induced histologic changes were not alter ed by NOS blockade with AG or L-NNA. We conclude that hyperoxic exposure of rat pups up-regulated both iNOS and eNOS and increased NO activity as meas ured by cGMP levels derived from both iNOS and eNOS. Blockade of NOS reduce d cGMP levels in the hyperoxic rat pups; however, it did not seem to revers e the pathologic consequences of hyperoxic exposure.