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British Journal of Anaesthesia 2007 98(4):484-490; doi:10.1093/bja/aem011
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

The {alpha}2-adrenergic receptor antagonist yohimbine improves endotoxin-induced inhibition of gastrointestinal motility in mice

N. Hamano, T. Inada*, R. Iwata, T. Asai and K. Shingu

Department of Anaesthesiology, Kansai Medical University, Osaka, Japan

* Corresponding author: Department of Anaesthesiology, Kansai Medical University, 10-15, Fumizono-cho, Moriguchi, Osaka 570-8507, Japan. E-mail: takefumi{at}wd5.so-net.ne.jp

Background: Sepsis inhibits gastrointestinal motility. Although the exact mechanism of this is unclear, lipopolysaccharide is known to activate macrophages in the gastrointestinal wall, which upregulate their expression of inducible nitric oxide synthase (iNOS). This leads to an increased production of nitric oxide, which relaxes the gastrointestinal muscles. We studied endotoxaemic mice to determine whether yohimbine improved delayed gastric emptying and gastrointestinal transit.

Methods: Male Balb/c mice (n = 49) were randomly allocated to two groups, and either yohimbine 25 µg or saline was injected s.c. Four hours later, mice in each group were further randomly allocated to two groups, and either lipopolysaccharide 100 µg or saline was injected intraperitoneally. Eight hours later, liquid containing fluorescent microbeads was infused into the stomach, and 30 min later, gastric emptying and gastrointestinal transit were measured using flow cytometry. We also studied whether yohimbine given after injection of lipopolysaccharide was effective (n = 22). In another group of mice (n = 32), iNOS in the gastrointestinal tract was measured using western blotting.

Results: Lipopolysaccharide significantly inhibited gastric emptying and gastrointestinal transit. Yohimbine, given before or after lipopolysaccharide, significantly attenuated the inhibitory effects of lipopolysaccharide. Lipopolysaccharide increased the expression of iNOS in the small intestine and yohimbine suppressed the effects of lipopolysaccharide.

Conclusions: In endotoxaemic mice, yohimbine improved delayed gastric emptying and gastrointestinal transit, possibly by downregulating lipopolysaccharide-induced increased expression of iNOS.

Keywords: complications, sepsis; critical care; gastrointestinal tract, emptying; gastrointestinal tract, transit; sympathetic nervous system, yohimbine


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