Toxic dilatation of colon in a rat model of colitis is linked to an inducible form of nitric oxide synthase.
The contribution of nitric oxide (NO) to the altered colonic contractility of acute colitis was investigated in the 2,4,6-trinitroben-zenesulfonic acid model. NO synthase was measured in colonic tissue; the effects of NO synthase inhibition on colonic contractility were studied in vitro and in vivo. Inducible NO synthase was not detected in normal colons, whereas inflamed colons showed high activity. Acute inflammation was associated with enlarged colonic perimeter. NO synthase inhibitors or selective inhibitors of the inducible enzyme prevented colonic dilatation. In vitro, contractile responses to KCl were lower in muscle from colitic than control rats. After NO synthase inhibition, however, no difference was observed between colitic and control muscle contractility. In vivo, intracolonic pressure was lower in colitic than in control rats. Selective inhibition of inducible NO synthase increased intracolonic pressure in colitic but not in control rats. In conclusion, NO generation by inducible enzymes impairs smooth muscle contractility in colitis and may be involved in the pathogenesis of toxic dilatation of the colon.
Mourelle
M
M
Digestive System Research Unit, Hospital General Vall d'Hebron, Barcelona, Spain.
Vilaseca
J
J
Guarner
F
F
Salas
A
A
Malagelada
J R
JR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology; D004106:Dilatation; D004195:Disease Models, Animal; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007042:Hypoxanthines / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009543:Nifedipine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid
D004791:Enzyme Inhibitors; D006146:Guanidines; D007042:Hypoxanthines; D003907:Dexamethasone; D014302:Trinitrobenzenesulfonic Acid; D001120:Arginine; D009195:Peroxidase; D019001:Nitric Oxide Synthase; C017202:2,4-diaminohypoxanthine; D009543:Nifedipine; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester