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NEUROREGULATION AND MOTILITY

₂-Adrenergic regulation of NO production alters postoperative intestinal smooth muscle dysfunction in rodents

Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261

Submitted 18 December 2003 ; accepted in final form 5 May 2004

₂-Adrenergic receptor activation plays an important role in the development of postoperative ileus. ₂-Adrenergic receptors also regulate nitric oxide (NO) production by the mononuclear phagocyte system. We have previously shown that intestinal manipulation leads to a significant increase in NO production by infiltrating monocytes within the intestinal muscularis. The purpose of this study was to investigate whether ₂-adrenergic blockade with yohimbine would alter postsurgical intestinal smooth muscle dysfunction and NO production by infiltrating monocytes and macrophages within the intestinal muscularis. Rats underwent small bowel intestinal manipulation with or without yohimbine. In vivo gastrointestinal transit and in vitro jejunal circular muscle contractility was measured 24 h postoperatively. RT-PCR was used to detect inducible NO synthase (iNOS) expression. NO levels in tissue culture supernatants were measured. Immunohistochemistry was used to localize ₂-adrenergic receptor expression in the intestinal muscularis. Yohimbine significantly decreased manipulation-induced delay in gastrointestinal transit and reversed the postoperative decrease in intestinal muscle contractility. Intestinal manipulation resulted in significant iNOS mRNA induction in the intestinal muscularis, which was markedly attenuated after yohimbine treatment. Yohimbine also significantly decreased the postoperative increase in NO released into intestinal muscularis tissue culture supernatant. Immunohistochemistry identified ₂-adrenergic receptors on monocytes recruited postoperatively into the intestinal muscularis. This study demonstrates that ₂-adrenergic receptor stimulation of the inflamed postoperative intestinal muscularis plays a significant role in aggravating postoperative ileus through an enhanced induction of iNOS mRNA and increased release of NO from manipulated intestinal muscularis.

yohimbine

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