Background
In animal models of postoperative ileus (POI), inflammation of the intestine plays
an important role in the pathogenesis of POI. Changes in α2-adrenoceptors and nitrergic regulation have been proposed to be implicated. The aim
of our study was to investigate the presynaptic α2-receptor–mediated 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 α2-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 α2-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.
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Article info
Publication history
Accepted:
May 17,
2008
Footnotes
Supported by Grant G.0053.02 from the Fund of Scientific Research Flanders, and by Interuniversity Attraction Poles Programme P5/20 (Federal Public Planning Service Science Policy).
Identification
Copyright
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
