Jejunal cholinergic, nitrergic, and soluble guanylate cyclase activity in postoperative ileusJejunal cholinergic, nitrergic, and soluble guanylate cyclase activity in postoperative ileus
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)
Laboratory of cell biology and histology
VIB DMG - Neurogenetics Group
2008St. Louis, Mo., 2008
Surgery. - St. Louis, Mo.
144(2008):3, p. 410-426
University of Antwerp
Background In animal models of postoperative ileus (POI), inflammation of the intestine plays an important role in the pathogenesis of POI. Changes in á2-adrenoceptors and nitrergic regulation have been proposed to be implicated. The aim of our study was to investigate the presynaptic á2-receptormediated control of cholinergic nerve activity, the nitrergic nerve activity, and the possible role of soluble guanylate cyclase (sGC) during the inflammatory phase of POI. Methods Ileus was induced by anesthesia and manipulation of the rat jejunum. Rats were treated with the sGC inhibitors methylene blue or ODQ; nonoperated animals served as controls. After 24 h, plasma and jejunal tissue were collected for biochemical assays, nitric oxide synthase-1 (NOS-1)-immunohistochemistry, acetylcholine (Ach)-release experiments, and muscle tension experiments. Results In all operated animal groups, myeloperoxidase activity was significantly increased, which indicates initiation of an inflammatory response. The á2-adrenoceptor agonist UK14,304 reduced electrically induced Ach-release similarly in operated and nonoperated animals. In strips of operated animals, electrically induced nitrergic relaxations were decreased, whereas relaxations induced by exogenous nitric oxide (NO) remained unchanged compared with control. The number of myenteric neurons and the percentage of NOS-1-positive neurons were not influenced. Plasmatic cyclic guanosine monophosphate (cGMP) levels were decreased in all operated groups, whereas jejunal cGMP levels were unchanged compared with nonoperated controls; treatment with sGC inhibitors did not reduce plasmatic cGMP levels. Conclusions This study demonstrates that presynaptic á2-receptor mediated control of intestinal cholinergic nerve activity is unchanged during manipulation-induced inflammation. However, this inflammation induces impaired nitrergic neurotransmission related to decreased NOS-1 activity in the nitrergic nerves.