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, invitro and invivo studies using lipopolysaccharide were used. In the invitro 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 invivo 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.
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