Expression of iNOS mRNA associated with suppression of colonic contraction in rat colitis.
OBJECTIVE
Nitric oxide (NO) synthesis and inducible NO synthase (NOS) expression are increased in colon of patients with inflammatory bowel disease (IBD) and associated with decreased contractility. The aim was to investigate which subtype of NOS that is activated in experimental colitis.


METHODS
Experimental colitis was induced in Sprague-Dawley rats by Escherichia coli endotoxin. Expression of different subtypes of NOS was compared in normal and inflamed colon using reverse transcriptase-polymerase chain reaction. In organ baths, isometric contractile responses to acetylcholine (ACh) were studied in the colon, before and after incubation with the NOS inhibitor; N(omega)-nitro-L-arginine methyl ester (L-NAME) and NO donor glyceryl trinitrate.


RESULTS
Inflammation decreased colonic contraction to ACh from a pD(2) value of 7.09 +/- 0.16 to 5.30 +/- 0.17 (P < 0.001), and reduced maximal response to ACh. Pre-treatment with L-NAME reversed contractility and shifted the pD(2) for ACh from 5.30 +/- 0.17 to 6.60 +/- 0.19 (P < 0.001) along with a normalized contraction efficacy. RT-PCR product of iNOS was obtained only in rats treated with endotoxin.


CONCLUSIONS
Expression of iNOS is increased in inflamed colonic tissue. The induced overproduction of NO is likely to be responsible for the decreased motility in colitis where NO is suggested to exert a suppressive tone on colonic contractility, which is reversed by blockade of the enzyme.
Lundberg
S
S
Department of Medicine, Unit of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden. Sofie.Lundberg@ki.se
Holst
M
M
Hellström
P M
PM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003092:Colitis / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000503:physiopathology; D004731:Endotoxins; D005769:Gastrointestinal Motility; D015870:Gene Expression; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D046509:Tissue Culture Techniques; D014665:Vasodilator Agents / Q000494:pharmacology
D004731:Endotoxins; D012333:RNA, Messenger; D014665:Vasodilator Agents; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D052247:Nitric Oxide Synthase Type II; D000109:Acetylcholine