Impaired nitrergic innervation in rat colitis induced by dextran sulfate sodium.
OBJECTIVE
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.
Mizuta
Y
Y
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Isomoto
H
H
Takahashi
T
T
D000818:Animals; D015153:Blotting, Western; D002384:Catalysis; D003092:Colitis / Q000139:chemically induced* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016264:Dextran Sulfate; D005769:Gastrointestinal Motility; D005772:Gastrointestinal Transit; D007150:Immunohistochemistry; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013869:Thiolester Hydrolases / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
D016264:Dextran Sulfate; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase