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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/L446    most recent 00412.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Itoh, T. Articles by Nagaya, N. Search for Related Content PubMed PubMed Citation Articles by Itoh, T. Articles by Nagaya, N.

Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats

¹Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka, Japan; ²Second Department of Internal Medicine, Nara Medical University, Nara, Japan; ³Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; and Departments of ⁴Biochemistry and ⁵Internal Medicine, National Cardiovascular Center, Osaka, Japan

Submitted 26 September 2005 ; accepted in final form 5 June 2007

Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 µg·kg^–1·min^–1) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)- and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF- and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.

apoptosis; hyperpermeability; inflammation

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