title: A spontaneous animal model of intestinal dysmotility evoked by inflammatory nitrergic dysfunction.
abstract: OBJECTIVE
  Recent reports indicate the presence of low grade inflammation in functional gastrointestinal disorders (FGID), in these cases often called "post-inflammatory" FGIDs. However, suitable animal models to study these disorders are not available. The Biobreeding (BB) rat consists of a diabetes-resistant (BBDR) and a diabetes-prone (BBDP) strain. In the diabetes-prone strain, 40-60% of the animals develop diabetes and concomitant nitrergic dysfunction. Our aim was to investigate the occurrence of intestinal inflammation, nitrergic dysfunction and intestinal dysmotility in non-diabetic animals.
  
  
  METHODS
  Jejunal inflammation (MPO assay, Hematoxylin&Eosin staining and inducible nitric oxide synthase (iNOS) mRNA expression), in vitro jejunal motility (video analysis) and myenteric neuronal numbers (immunohistochemistry) were assessed in control, normoglycaemic BBDP and diabetic BBDP rats. To study the impact of iNOS inhibition on these parameters, normoglycaemic BBDP rats were treated with aminoguanidine.
  
  
  RESULTS
  Compared to control, significant polymorphonuclear (PMN) cell infiltration, enhanced MPO activity, increased iNOS mRNA expression and a decreased ratio of nNOS to Hu-C/D positive neurons were observed in both normoglycaemic and diabetic BBDP rats. Aminoguanidine treatment decreased PMN infiltration, iNOS mRNA expression and MPO activity. Moreover, it restored the ratio of nNOS to Hu-C/D positive nerves in the myenteric plexus and decreased the abnormal jejunal elongation and dilation observed in normoglycaemic BBDP rats.
  
  
  CONCLUSIONS
  Aminoguanidine treatment counteracts the inflammation-induced nitrergic dysfunction and prevents dysmotility, both of which are independent of hyperglycaemia in BB rats. Nitrergic dysfunction may contribute to the pathophysiology of "low-grade inflammatory" FGIDs. Normoglycaemic BBDP rats may be considered a suitable animal model to study the pathogenesis of FGIDs.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Masaoka
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Vanuytsel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanormelingen
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Kindt
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Shadea
authors.initials: S
authors.lastname: Salim Rasoel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Werend
authors.initials: W
authors.lastname: Boesmans
authors.affiliation: Department of Pathology, University of Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Ricard
authors.initials: R
authors.lastname: Farré
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vanden Berghe
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006943:Hyperglycemia / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D007422:Intestines / Q000276:immunology* / Q000503:physiopathology*; D007583:Jejunum / Q000276:immunology / Q000503:physiopathology; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000503:physiopathology; D009197:Myenteric Plexus / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism
chemical_list: D052247:Nitric Oxide Synthase Type II