title: Nitric oxide-mediated injury of interstitial cells of Cajal and intestinal dysmotility under endotoxemia of mice.
abstract: Gastrointestinal dysmotility is frequently observed under septic conditions, yet its precise mechanisms remain to be elucidated. In this study, we have investigated the mechanisms of intestinal dysmotility by lipopolysaccharides (LPS) and the role of the interstitial cells of Cajal (ICCs) in motility disorders using a mouse endotoxin model. The injection of LPS caused time- and dose-dependent decreases in the intestinal contractility, which was associated with similar time- and dose-dependent decreases in the number of KIT-positive fibroblast-like cells located in the intermuscular layer. iNOS inhibitors, L-NAME and aminoguanidine (AG), but not 7-nitroindazole (7NI), a specific nNOS inhibitor, inhibited the LPS-induced decreases in both the contractility and the number of KIT-positive cells. A spontaneous NO releaser, FK409, not only diminished spontaneous electrical potential and phasic contractions, but also decreased the number of KIT-positive cells. Pretreatment with gadolinium inhibited the activation of macrophages and the induction of iNOS in intestinal resident macrophages, and restored the number of KIT-positive cells and intestinal contractions. These results suggested that NO produced from intestinal macrophages via iNOS induced by LPS, may be involved in the ICCs injury and intestinal dysmotility under septic conditions.
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Ueshima
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000473:pathology*; D005682:Gadolinium / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D056885:Interstitial Cells of Cajal / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism
chemical_list: D006146:Guanidines; D007191:Indazoles; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D005682:Gadolinium; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C004479:pimagedine; C080122:7-nitroindazole