Impaired nitrergic innervation in rat colitis induced by dextran sulfate sodium

Gastroenterology. 2000 Apr;118(4):714-23. doi: 10.1016/s0016-5085(00)70141-7.


Background & aims: The pathophysiological role of neuronal nitric oxide synthase (nNOS) in colitis remains unknown.

Methods: We investigated colonic transit, nonadrenergic, noncholinergic (NANC) relaxation, nNOS activity, and nNOS synthesis in the myenteric plexus in dextran sulfate sodium (DSS)-induced colitis in rats.

Results: Oral administration of 5% DSS for 7 days induced predominant distal colitis and delayed colonic transit. In the proximal colon, carbachol-, sodium nitroprusside-, and electrical field stimulation (EFS)-induced responses were not different between control and DSS-treated rats. In the distal colon, EFS-evoked cholinergic contraction, NANC relaxation, and orphanin FQ-induced contraction were significantly impaired in DSS-treated rats compared with those in control rats, but carbachol- and sodium nitroprusside-induced responses remained intact in DSS-treated rats. The number of nNOS-immunopositive cells, catalytic activity of NOS, and nNOS synthesis in the colonic wall were significantly reduced in the distal colon of DSS-treated rats. In contrast, the number of PGP 9.5-immunopositive cells and PGP 9.5 synthesis in the colonic wall remained intact in the distal colon of DSS-treated rats.

Conclusions: These results suggest that impaired NANC relaxation in the distal colon is associated with reduced activity and synthesis of nNOS in the myenteric plexus in DSS-induced colitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Catalysis
  • Colitis / chemically induced*
  • Colitis / enzymology*
  • Colitis / pathology
  • Colitis / physiopathology
  • Colon / metabolism
  • Colon / pathology
  • Colon / physiopathology
  • Dextran Sulfate*
  • Gastrointestinal Motility
  • Gastrointestinal Transit
  • Immunohistochemistry
  • Male
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type I
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Thiolester Hydrolases / metabolism
  • Ubiquitin Thiolesterase


  • Dextran Sulfate
  • Peroxidase
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • Thiolester Hydrolases
  • Ubiquitin Thiolesterase