THE ROLE OF NITRIC OXIDE IN HYPEROXIC LUNG
INJURY IN PREMATURE RATS
Ma LY, Chang LW, Zhang XH,
ChenY
Department
of Pediatrics, Tongji Hospital, Tongji Medical College, Huzhong University
of Science and Technology, Wuhan, China
Objective: To investigate the role of nitric oxide
(NO) in hyperoxic lung injury
Methods: the 3-day-old preterm
rats were randomly assigned: group I (hyperoxia group), group II (hyperoxia +Nw-nitro- L- arginine methyl
ester (L-NAME) group), group III (air group), group IV (air+L-NAME group).
Group I and II were exposed to ³90％O2 for 3 or 7
days. Group II and IV received subcutaneous L-NAMEy on daily basis
(20mg/kg). After 3 days or 7 days exposure, the lung wet weight/dry weight
ratio (W/D), total protein and malondialdehyde (MDA) in bronchoalveolar
lavage fluid (BALF) and lung morphometry were examined in all groups. NO
content, expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in
lungs were measured in group I and III.
Results: after 3 days exposure,
group I appeared acute lung injury; after 7 days exposure, except MDA,
total protein and W/D were also increased in comparison with group III (P<0.01, 0.05), pathologic changes
were more severe than those after 3 days exposure. After 3 and 7 days
exposure, total protein in group II was significantly increased as compared
with group I (P<0.01 for
both). The pulmonary acute inflammatory changes were more obvious in group
II than in group I. BALF
protein content in group IV was higher than that in group III after 7 days
exposure (P<0.01). After 3 and 7 days exposure, NO content in BALF
were all significantly elevated in group I as compared with group III (P<0.01 for all). In the lungs of
group I, strong immunostaining for iNOS was observed in airway and alveolar
epithelium, inflammatory cells, which were stronger than those in group
III. Expression of iNOS in rats after 7 days hyperoxic exposure was
stronger than that after 3 days exposure; Shortly after 7 days exposure,
stronger immunostaining for eNOS in airway epithelium in group I than that
in group III was seen.
Conclusion: L-NAME worsened acute
hyperoxic lung injury in preterm rats. Hyperoxia can significantly
upregulate the expression of iNOS and eNOS in inflammatory cells, epithelium
in the lungs of preterm rats, promote NO generation. NO may have dual roles in pulmonary
oxygen toxicity.