Cited by 70Inflammatory Bowel DiseaseNitric Oxide and Endothelin EffectsInflammatory mediators and NSAID effects

Increased disease activity in eNOS-deficient mice in experimental colitis

Sasaki, M, Bharwani, S, Jordan, P, Elrod, J.W, Grisham, M.B, Jackson, T.H, Lefer, D.J, Alexander, J.Steven·2003·Free Radical Biology and Medicine

Abstract

Oral dextran sodium sulfate (DSS, 3%) produces experimental colitis with many features of human inflammatory bowel disease (IBD), (leukocyte extravasation, cachexia, and histopathology). Previous studies suggest that the inducible nitric oxide synthase (iNOS) in blood cells or in the endothelium contribute to this injury. However, until now no study has been performed to directly evaluate the role of endothelial nitric oxide synthase (eNOS) in IBD. We compared disease activity in wild-type (eNOS+/+) and eNOS-deficient (eNOS-/-) mice in the DSS model of colitis. Administration of DSS induced weight loss, stool blood, and overt histopathology in both mouse strains. Disease activity was dramatically increased in eNOS-/- mice compared to wild types. Histologically, eNOS-deficient mice had greater leukocyte infiltration, gut injury, and expressed higher levels of the mucosal addressin, MAdCAM-1. These results demonstrate that eNOS plays an important role in limiting injury to the intestine during experimental colitis and altered eNOS content and/or activity may contribute to human IBD.

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Crossref · 10.1016/j.freeradbiomed.2003.09.016

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Authors
Sasaki, M., Bharwani, S., Jordan, P., Elrod, J. W., Grisham, M. B., Jackson, T. H., Lefer, D. J., & Alexander, J. S.
Affiliations
Louisiana State University Health Sciences Center Shreveport (US)
Corresponding author
Alexander, J.Steven
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2003-12
Volume
35
Issue
12
Pages
1679-1687
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2069037824
Cited by
70
References
56
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 6 · 2012: 3
FWCI
2.65
Type
journal article
Language
en
Open access
closed
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r29hl047615-05)
  • National Heart, Lung, and Blood Institute (HL-47615)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P02-DK-43785)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords
endothelial nitric oxide synthase, eNOS-deficient mice, experimental colitis, DSS-induced colitis, inflammatory bowel disease, disease activity, leukocyte infiltration, MAdCAM-1, intestinal injury, nitric oxide
MeSH terms
Animals, Colitis, Colon, Immunoglobulins, Immunohistochemistry, Mucoproteins, Cell Adhesion Molecules, Mice, Knockout, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III

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