Atrial natriuretic peptide inhibits lipopolysaccharide-induced acute lung injury.
OBJECTIVE
We recently reported that administration of atrial natriuretic peptide during the perioperative period has prophylactic effects with respect to not only cardiovascular but also respiratory complications following pulmonary resection. However, its mechanisms are not well understood. The objective of the present study was to investigate the mechanism of the prophylactic effects of atrial natriuretic peptide in an acute lung injury model.


METHODS
For the evaluation of the early phase of pulmonary inflammation, in vitro and in vivo studies using lipopolysaccharide were used. In the in vitro study, the effects of atrial natriuretic peptide on the induction of E-selectin by lipopolysaccharide in human pulmonary artery endothelial cells were evaluated. In the in vivo study, the effects of atrial natriuretic peptide on lipopolysaccharide-induced inflammatory cell infiltration and cytokine levels including tumor necrosis factor-alpha and interleukin-6 in the bronchoalveolar lavage fluid in the lungs of C57/B6 mice were examined. The number of myeloperoxidase-positive staining cells in the tissue sections of the lung of lipopolysaccharide-administered C57/B6 mice was also evaluated.


RESULTS
Atrial natriuretic peptide significantly attenuated the up-regulation of E-selectin expression induced by lipopolysaccharide in human pulmonary artery endothelial cells. There were significantly lower cell counts and levels of tumor necrosis factor-alpha and interleukin-6 in the bronchoalveolar lavage fluid of atrial natriuretic peptide-treated mice compared to control mice after lipopolysaccharide injection. In addition, there were significantly fewer myeloperoxidase-positive cells in atrial natriuretic peptide-treated mice than in control mice after lipopolysaccharide injection.


CONCLUSIONS
Atrial natriuretic peptide had a protective effect in the lipopolysaccharide-induced acute lung injury model. Atrial natriuretic peptide may be of value in therapeutic strategies aimed at the treatment of acute lung injury such as pneumonia or acute respiratory distress syndrome.
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan; Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan. Electronic address: nojiri@ri.ncvc.go.jp.
Takashi
T
Nojiri
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita-City, Osaka, Japan.
Hiroshi
H
Hosoda
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan.
Takeshi
T
Tokudome
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita-City, Osaka, Japan.
Koichi
K
Miura
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan.
Shin
S
Ishikane
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Toru
T
Kimura
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Yasushi
Y
Shintani
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Masayoshi
M
Inoue
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Noriyoshi
N
Sawabata
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan.
Mikiya
M
Miyazato
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka, Japan.
Meinoshin
M
Okumura
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Suita-City, Osaka, Japan.
Kenji
K
Kangawa
D055371:Acute Lung Injury / Q000517:prevention & control*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D019040:E-Selectin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009320:Atrial Natriuretic Factor
Acute lung injury; Atrial natriuretic peptide; Pulmonary inflammation