Neurogastroenterology and motility, 2011-07, Vol.23 (7), p.666-e278
2011
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- Autor(en) / Beteiligte
- Titel
- Role of neuronal nitric oxide synthase in colonic distension‐induced hyperalgesia in distal colon of neonatal maternal separated male rats
- Ist Teil von
- Neurogastroenterology and motility, 2011-07, Vol.23 (7), p.666-e278
- Ort / Verlag
- Oxford, UK: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Background Nitric oxide (NO) is implicated in the pathogenesis of irritable bowel syndrome (IBS) but the underlying mechanism is unclear. Thus, the aim of the present study is to examine the role of NO synthase (NOS) expression in the distal colon of neonatal maternal separation (NMS) model rats employed in IBS studies. Methods Male neonates of Sprague‐Dawley rats were randomly assigned into NMS and normal control (N) groups. Rats of NMS group were subjected to 3 h daily maternal separation on postnatal day 2–21. Rats were administrated non‐selective NOS inhibitor l‐NAME (100 mg kg−1), selective neuronal NOS (nNOS) inhibitor 7‐NINA (10 mg kg−1), selective inducible NOS (iNOS) inhibitor, endothelial NOS (eNOS) inhibitor (10 mg kg−1) or Vehicle (Veh; distilled water) intraperitoneally 1 h prior to the experiment for the test and control groups, respectively. Key Results The amount of NO was significantly higher in the NMS Veh rats compared with unseparated N rats. Western‐blotting and real‐time quantitative PCR studies showed that protein and mRNA expression of nNOS were higher in the NMS group than that in the N rats; whereas no significant change in iNOS and eNOS was found in either groups. Neonatal maternal separation Veh rats showed low pain threshold and increased electromyogram (EMG) activity in response to colonic distension stimuli. l‐NAME and 7‐Nitroindazole monosodium salt (7‐NINA) increased pain threshold pressure and attenuated EMG activity in the NMS rats. In addition, l‐NAME and 7‐NINA substantially reduced oxidative marker malondialdehyde level in NMS rats. Conclusions & Inferences Neonatal maternal separation increased the NO generation by nNOS upregulation that interact with reactive oxygen species contributing to the visceral hypersensitivity in IBS.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1350-1925eISSN: 1365-2982DOI: 10.1111/j.1365-2982.2011.01697.xTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3117987
- Format
- –
- Schlagworte
- Animals, Animals, Newborn - physiology, Colon, Colon - physiopathology, Colonic Diseases - physiopathology, colonic distension, Disease Models, Animal, distal colon, Distension, Electromyography, EMG, Gastrointestinal Motility - physiology, Gene expression, Hyperalgesia - physiopathology, Hypersensitivity, Indazoles - pharmacology, Irritable bowel syndrome, Irritable Bowel Syndrome - physiopathology, Male, Malondialdehyde, Maternal Behavior - physiology, neonatal maternal separation, Neonates, NG-Nitroarginine methyl ester, NG-Nitroarginine Methyl Ester - pharmacology, Nitric oxide, Nitric Oxide Synthase Type I - antagonists & inhibitors, Nitric Oxide Synthase Type I - drug effects, Nitric Oxide Synthase Type I - physiology, Nitric Oxide Synthase Type II - antagonists & inhibitors, Nitric Oxide Synthase Type II - drug effects, Nitric Oxide Synthase Type II - physiology, Nitric Oxide Synthase Type III - antagonists & inhibitors, Nitric Oxide Synthase Type III - drug effects, Nitric Oxide Synthase Type III - physiology, Nitric-oxide synthase, Oxidative Stress - drug effects, Pain perception, Polymerase chain reaction, Pressure, Rats, Rats, Sprague-Dawley, Reactive oxygen species, Salts, Stress, Psychological - physiopathology, visceral hyperalgesia