The alpha2-adrenergic receptor antagonist yohimbine improves endotoxin-induced inhibition of gastrointestinal motility in mice.
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 microg or saline was injected s.c. Four hours later, mice in each group were further randomly allocated to two groups, and either lipopolysaccharide 100 microg 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.
Hamano
N
N
Department of Anaesthesiology, Kansai Medical University, Osaka, Japan.
Inada
T
T
Iwata
R
R
Asai
T
T
Shingu
K
K
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D007421:Intestine, Small / Q000201:enzymology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D008070:Lipopolysaccharides; D015016:Yohimbine; D052247:Nitric Oxide Synthase Type II