Inhaled nitric oxide increases endothelial permeability in Pseudomonas aeruginosa pneumonia.
OBJECTIVE
Pneumonia is a frequent cause of acute respiratory distress syndrome (ARDS), and Pseudomonas aeruginosa is a leading pathogen in nosocomial pneumonia. The management of ARDS remains a major problem, and only a limited number of options can improve the oxygenation. Inhaled nitric oxide (iNO) has been widely used, although this molecule is a free radical potentially harmful through the generation of toxic radical derivatives. The goal of our study was to assess the consequences of iNO (10 ppm) in a rat model of P. aeruginosa-induced lung injury.


METHODS
The animals were exposed for 24 h to iNO after instillation of the pathogen. Distal alveolar fluid clearance (DAFC) and epithelial and endothelial permeability were measured with a double flux of radio-labeled albumin.


RESULTS
DAFC and epithelial permeability were increased in pneumonia but not influenced by iNO. In contrast, endothelial permeability was statistically significantly higher in the pneumonic animals exposed to iNO than in the pneumonic group without iNO (0.24+/-0.03 vs 0.47+/-0.1, p<0.05). This increase was not related to the production of nitrate/nitrite, nor to the increase of the inflammatory response evaluated by cytokine levels in the bronchoalveolar lavage fluid (TNF-alpha, IL-6, IL-10). The alveolar recruitment of polymorphonuclear neutrophils was comparable in the pneumonic group exposed to iNO and the pneumonic group without iNO.


CONCLUSIONS
iNO increases the endothelial permeability in P. aeruginosa pneumonia. The mechanism is not related to the production of nitrate/nitrite or to a greater inflammatory response.
Ader
Florence
F
EA 2689, Faculté de Médecine de Lille, Université de Lille II, 59045, Lille Cedex, France.
Le Berre
Rozenn
R
Lancel
Steve
S
Faure
Karine
K
Viget
Nathalie B
NB
Nowak
Emmanuel
E
Nevière
Rémi
R
Guery
Benoit P
BP
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D007958:Leukocyte Count; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology* / Q000627:therapeutic use; D018410:Pneumonia, Bacterial / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism
D001993:Bronchodilator Agents; D016207:Cytokines; D009569:Nitric Oxide