Inhaled nitric oxide attenuates hyperoxic and inflammatory injury without alteration of phosphatidylcholine synthesis in rat lungs.
We hypothesized that inhaled nitric oxide (iNO), a selective vasodilator for pulmonary hypertension, may exacerbate hyperoxia-related lung inflammatory injury by alteration of phosphatidylcholine (PC) synthesis in mature lungs. Healthy adult rats were allocated to 4 groups and exposed to: 95% oxygen, or 20ppm iNO, or both (ONO), or room air, all for 48h. (3)H-choline chloride was injected i.v. at 10min, 8, 16, and 24h prior to the end of 48h exposure and the animal lungs were processed. In oxygen group, oxidative damage and inflammation were significantly induced compared to the room air group. In ONO group there were significantly elevated glutathione, attenuated malondialdehyde, myeloperoxidase, and wet-to-dry lung weight ratio in lung parenchyma, decreased white cell counts and vascular-to-alveolar leakage of albumin in bronchoalveolar lavage fluid. In both oxygen and ONO groups both total phospholipids and surfactant protein-A were significantly increased compared with the room air group. Newly synthesized (3)H-PC was low in the lungs of NO group but high over time in both oxygen and ONO groups. Morphologically, lung injury was mild in ONO, but moderate in both oxygen and NO groups. We conclude that iNO alleviated oxidative damage and inflammation, and reduced alveolar leakage in hyperoxic injury of the mature lungs. Hyperoxia enhanced production of surfactant, whereas iNO did not attenuate this effect.
Hu
Xiaowei
X
Laboratory of Respiratory and Intensive Care Medicine, Children's Hospital of Fudan University, 183 Feng Lin Road, Shanghai 200032, PR China.
Guo
Chunbao
C
Sun
Bo
B
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D018496:Hyperoxia / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
D001993:Bronchodilator Agents; D016328:NF-kappa B; D010713:Phosphatidylcholines; D037662:Pulmonary Surfactant-Associated Protein A; C017463:lecithins, disaturated; D009569:Nitric Oxide; D008315:Malondialdehyde; D009195:Peroxidase; D005979:Glutathione Peroxidase; D005978:Glutathione