Nitric Oxide Inhalation Inhibits Pulmonary Inducible NO Synthase but Not Nitrotyrosine Formation and Cell Apoptosis in Rat Lungs Following Meconium Aspiration
Meiping Lu, Lizhong Du, Xiangxiang Chen, Weizhong Gu, Zhenzhu Yu.
BACKGROUND: Inhaled nitric oxide (iNO) has been successfully used in neonatal persistent pulmonary hypertension and hypoxemic respiratory failure.But the role of iNO in acute lung injury(ALI) following meconium aspiration has not yet been established.
OBJECTIVE: To investigate the effects of iNO on the pulmonary inflammation and peroxidation and protein nitration in a rat model of ALI following meconium aspiration.
DESIGN/METHODS: Twenty-four health male SD rats were studied in three groups (n=8): meconium-induced ALI with intratracheal instillation of 1ml/kg saline (Mec/saline group) or continuous inhalation of NO at 20ppm (Mec/iNO group), and the control group was intratracheally instilled 1ml/kg saline. Rats were killed in 24hrs after treatment. Lung tissue samples were studied histologically for lung injury score, electron microscopy for apoptotic cell death, TUNEL for the detection of the DNA fragmentation in pulmonary apoptotic cells expressed as apoptotic index (AI), western blot for pulmonary inducible NO synthase (iNOS) and RT-PCR for IL-1β mRNA expression. Nitrotyrosine formation, bronchoalveolar lavage (BAL) cell count, pulmonary MPO activity and MDA were also examined.
RESULTS: Compared with the control, a significant increase in the expressions of iNOS protein and IL-1β mRNA was found in the Mec/saline group (P < 0.01 respectively). BAL cell count, MPO activity, lung injury score, pulmonary AI, MDA levels and nitrotyrosine formation were also increased significantly (P < 0.01 respectively). Compared with Mec/saline group, NO inhalation significantly inhibited the meconium-induced iNOS protein and IL-1β mRNA expressions (P < 0.01 respectively). BAL cell count, MPO activity and lung injury score were also significantly decreased (P < 0.01, 0.01, or 0.05 respectively). However, there were no statistical differences in MDA level, nitrotyrosine formation or pulmonary AI between Mec/saline and Mec/iNO groups. Electron microscopy revealed a significant number of epithelial apoptosis both in rat lung of Mec/saline and Mec/iNO groups.
CONCLUSIONS: The results thus suggest that inflammatory injury and NO-superoxide pathway as well as epithelial apoptosis are involved in the meconium-induced ALI. Early continuous 20ppm NO inhalation may protect the lung from inflammatory injury, but might not decrease epithelial apoptosis and lung nitrotyrosine formation.
PAS 2005: 57: 2410
Tuesday, May 17, 2005 10:30 am, Washington Convention Center - Room 207 A
Platform Session: Global Perspectives on Birth Asphyxia, Part II (10:30 AM - 12:30 PM)
Course Number: 7350