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eNOS involved in colitis-induced mucosal blood flow increase
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2007 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 293, no 6, G1281-G1287 p.Article in journal (Refereed) Published
Abstract [en]

The role of NO in inflammatory bowel disease is controversial. Studies indicate that endothelial nitric oxide synthase (eNOS) might be involved in protecting the mucosa against colonic inflammation. The aim of this study was to investigate the involvement of nitric oxide (NO) in regulating colonic mucosal blood flow in two different colitis models in rats. In anesthetized control and colitic rats, the distal colon was exteriorized and the mucosa visualized. Blood flow (laser-Doppler flowmetry) and arterial blood pressure were continuously monitored throughout the experiments, and vascular resistance was calculated. Trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) was used to induce colitis. All groups were given the NOS inhibitor N-omega-nitro-Larginine (L-NNA) or the inducible NOS (iNOS) inhibitor L-N-6-(1-iminoethyl)- lysine (L-NIL). iNOS, eNOS, and neuronal NOS (nNOS) mRNA in colonic samples were investigated with real-time RT-PCR. Before NOS inhibition, colonic mucosal blood flow, expressed as perfusion units, was higher in both colitis models compared with the controls. The blood flow was reduced in the TNBS- and DSS-treated rats during L-NNA administration but was not altered in the control group. Vascular resistance increased more in the TNBS- and DSS-treated rats than in the control rats, indicating a higher level of vasodilating NO in the colitis models. L-NIL did not alter blood pressure or blood flow in any of the groups. iNOS and eNOS mRNA increased in both colitis models, whereas nNOS remained at the control level. TNBS- and DSS-induced colitis results in increased colonic mucosal blood flow, most probably due to increased eNOS activity.

Place, publisher, year, edition, pages
2007. Vol. 293, no 6, G1281-G1287 p.
Keyword [en]
trinitrobenzene sulfonic acid, dextran sulfate sodium, inducible nitric oxide synthase, neuronal nitric oxide synthase
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-13069DOI: 10.1152/ajpgi.00357.2007ISI: 000251510500020PubMedID: 17947450OAI: oai:DiVA.org:uu-13069DiVA: diva2:40839
Available from: 2008-01-21 Created: 2008-01-21 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Microcirculation, Mucus and Microbiota in Inflammatory Bowel Disease
Open this publication in new window or tab >>Microcirculation, Mucus and Microbiota in Inflammatory Bowel Disease
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inflammatory bowel diseases, (IBD), are a group of chronic disorders of the gastro-intestinal tract, and include Crohn’s disease (CD) and Ulcerative Colitis (UC). The pathogenesis is not known, but involves at least in part a loss of tolerance towards the commensal colonic microbiota. In this thesis, we show in animal models of CD and UC that the colonic mucosal blood flow increased compared to healthy animals. This blood flow increase is due to an up regulation of endothelial nitric oxide synthase (NOS). Further, we show in the UC model that the thickness of the firmly adherent colonic mucus layer increased compared to healthy animals. This increase is due to an up regulation of inducible NOS in the epithelium. Both the blood flow and mucus thickness increase appear to be protective mechanisms.  We demonstrate that the firmly adherent colonic mucus layer acts as a partial barrier towards luminal bacteria. In the UC model, this barrier is destroyed, causing increased bacterial translocation. The adhesion molecule P-selectin was up regulated in the UC model, leading to increased interactions between leukocytes and the endothelium, but also increased interactions between platelets and the endothelium. This indicates that not only leukocytes, but also platelets are involved in colonic inflammation. The addition of the probiotic bacterial strain Lactobacillus reuteri prevented disease by normalizing P-selectin levels and endothelial interactions with leukocytes and platelets. Lactobacillus reuteri also decreased bacterial translocation over the epithelium. In summary, this thesis highlights the importance of colonic barrier functions, and investigates the role of the microbiota in experimental IBD.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 516
Keyword
inflammatory bowel diseases, experimental colitis, DSS, TNBS, colonic mucosal blood flow, laser-doppler flowmetry, colonic mucus thickness, MUC2, colonic mucosal barrier function, iNOS, eNOS, probiotics, Lactobacilli, Lactobacillus reuteri, colonic microbiota, T-RFLP, bacterial translocation, intravital microscopy, P-selectin, leukocyte recruitment, platelet recruitment
National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:uu:diva-112718 (URN)978-91-554-7710-3 (ISBN)
Public defence
2010-03-06, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 13:15 (Swedish)
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Supervisors
Available from: 2010-02-12 Created: 2010-01-19 Last updated: 2010-02-12Bibliographically approved

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Petersson, JoelSchreiber, OlofPhillipson, MiaHolm, Lena

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