CHARACTERIZATION OF NITRIC-OXIDE SYNTHASE ACTIVITY IN THE RAT COLONIC MUCOSA AND MUSCLE AFTER ENDOTOXIN AND IN A MODEL OF COLITIS

Increases in nitric oxide synthase (NOS) activity 4 h after endotoxin (3 mg kg(-1) i.v.) were greater in colonic mucosa than in muscle and were calcium-independent in mucosa but calcium-dependent in the muscle. Induction of NOS in both tissues was prevented by dexamethasone (1 mg kg(-1) s.c.). Hence, these increases in NOS activity may represent distinct inducible NOS isoforms. In colitis produced by intracolonic trinitrobenzene sulphonic acid, initial colonic damage was accompanied by induction of calcium-independent NOS. In contrast, the later colonic healing was accompanied by an increase in calcium-dependent NOS activity, which may represent constitutive NOS activity associated with tissue regeneration. Excessive NO production by inducible NOS in the colonic mucosa after LPS and in colitis is likely to play an important role in the vascular damage, whilst increased synthesis of NO in colonic muscle may produce motility changes.