Jejunal cholinergic, nitrergic, and soluble guanylate cyclase activity in postoperative ileus.
BACKGROUND
In animal models of postoperative ileus (POI), inflammation of the intestine plays an important role in the pathogenesis of POI. Changes in alpha(2)-adrenoceptors and nitrergic regulation have been proposed to be implicated. The aim of our study was to investigate the presynaptic alpha(2)-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 alpha(2)-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 alpha(2)-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.
Vanneste
Gwen
G
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Van Nassauw
Luc
L
Kalfin
Reni
R
Van Colen
Inge
I
Elinck
Ellen
E
Van Crombruggen
Koen
K
Timmermans
Jean-Pierre
JP
Lefebvre
Romain A
RA
D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D007418:Intestinal Pseudo-Obstruction / Q000378:metabolism*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D026602:Nitrergic Neurons / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D008751:Methylene Blue