Role of N-methyl-D-aspartate receptor in hyperoxia-induced lung injury.
Glutamate (Glu) N-methyl-D-aspartate (NMDA) receptor is present in the lungs, and NMDA receptor antagonist MK-801 attenuates oxidant lung injury. We hypothesized that Glu excitotoxicity may participate in the pathogenesis of hyperoxia-induced lung injury. To determine possible pulmonary protective effects, we administered 0.05 ml/kg MK-801 or saline intraperitoneally daily to neonatal rats exposed to more than 95% oxygen in air. After 7 days, MK-801 decreased the hyperoxia-associated elevation of wet-to-dry lung weight, total leukocyte and neutrophil counts, total protein and lactate dehydroase in BAL fluid, total myeloperoxidase activity, and lung pathological injury. MK-801 inhibited hyperoxia-associated increments in reactive oxygen species production and NF-kappaB production. Hence, NMDA receptor antagonist MK-801 ameliorates hyperoxia-induced lung injury in neonatal rats, and is associated with decreased reactive oxygen species and NF-kappaB. We conclude that Glu may play an important role in hyperoxia-induced lung injury by activation of NMDA receptor.
Tang
FeiGe
F
Department of Pediatrics, XinHua Hospital, Shanghai Second Medical University, Shanghai, China.
Yue
ShaoJie
S
Luo
ZiQiang
Z
Feng
DeYun
D
Wang
Ming
M
Qian
Chen
C
Zhen
XiangRong
X
Duan
YuanDong
Y
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018496:Hyperoxia / Q000378:metabolism / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists; D016328:NF-kappa B; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011506:Proteins; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; C063447:p65 oncofetal mRNA transport protein, rat; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase