Impaired nitrergic innervation in rat colitis induced by dextran sulfate sodium

Abstract

Background & Aims: 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. GASTROENTEROLOGY 2000;118:714-723