Increased expression of an inducible isoform of nitric oxidesynthase and the formation of peroxynitrite in colonic mucosa ofpatients with active ulcerative colitis

Background—Increased production of reactivemetabolites of oxygen and nitrogen has been implicated in chronicinflammation of the gut. The object of this study was to examine themagnitude and location of nitric oxide synthase (NOS) activity andperoxynitrite formation in the colonic mucosa of patients withulcerative colitis in relation to the degree of inflammation.
Subjects—Thirty three patients with activeulcerative colitis (17 with mild or moderate inflammation, 16 withsevere inflammation).
Methods—Inducible NOS activity was determined inthe colonic mucosa by measuring the conversion ofL-arginine to citrulline in the absence of calcium. Thelocalisation of NOS and nitrotyrosine immunoreactivity was assessedimmunohistochemically using the labelled streptavidin biotin method.
Results—Inducible NOS activity increased inparallell with the degree of inflammation of the mucosa. Expression ofinducible NOS was found not only in the lamina propria, but also in the surface of the epithelium. Peroxynitrite formation as assessed bynitrotyrosine staining was frequently observed in the lamina propria ofactively inflamed mucosa.
Conclusions—Nitric oxide and peroxynitriteformation may play an important role in causing irreversible cellularinjury to the colonic mucosa in patients with active ulcerative colitis.

Keywords:nitric oxide; peroxynitrite; nitricoxide synthase; ulcerative colitis; colonic mucosa