Atrial natriuretic peptide inhibits lipopolysaccharide-induced acute lung injury

• Published in: Pulmonary pharmacology & therapeutics Vol. 29; no. 1; pp. 24 - 30
• Main Authors: Nojiri, Takashi, Hosoda, Hiroshi, Tokudome, Takeshi, Miura, Koichi, Ishikane, Shin, Kimura, Toru, Shintani, Yasushi, Inoue, Masayoshi, Sawabata, Noriyoshi, Miyazato, Mikiya, Okumura, Meinoshin, Kangawa, Kenji
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2014
• Subjects: Acute lung injury; Acute Lung Injury - prevention & control; Animals; Atrial Natriuretic Factor - pharmacology; Atrial natriuretic peptide; Bronchoalveolar Lavage Fluid; Disease Models, Animal; E-Selectin - genetics; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Humans; Interleukin-6 - metabolism; Lipopolysaccharides - toxicity; Lung - cytology; Lung - drug effects; Lung - pathology; Medical Education; Mice; Mice, Inbred C57BL; Pulmonary Artery - drug effects; Pulmonary Artery - metabolism; Pulmonary inflammation; Pulmonary/Respiratory; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation - drug effects; CINC-1; MCP-1; ANP; MIP-2; monocyte chemoattractant protein-1; Atrial natriuretic peptide; HPAEC; MPO; interleukin-6; LPS; mitogen-activated protein kinase; tumor necrosis factor-alpha; NF-κB; macrophage inflammatory protein-2; Pulmonary inflammation; hematoxylin–eosin; Acute lung injury; cytokine-induced neutrophil chemoattractant-1; VEGF; nuclear factor-kappa B; guanylyl cyclase-A; myeloperoxidase; MAPK; BAL; human pulmonary artery endothelial cells; IL-6; GC-A; TNF-α; vascular endothelial growth factor; lipopolysaccharide; bronchoalveolar lavage; HE
• ISSN: 1094-5539; 1522-9629
• DOI: 10.1016/j.pupt.2014.01.003

Abstract Objectives 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.