Nitric oxide: The Jekyll and Hyde of gut inflammation

Abstract

We studied the effects of seven day treatment with the nitric oxide synthase (NOS) inhibitorN ^G-nitro-l-arginine (l-NAME), administered in the drinking water (100 μg/mlad lib) of female guinea pigs. The effects of NOS inhibition were evaluated in naive animals and in guinea pigs with ileitis induced by intraluminal trinitrobenzenesulfonic acid (TNBS). After 7 days, animals were anesthetized, a sterile saline lavage injected into an ileal loop and removed after 30 min for analysis. In naive guinea pigs,l-NAME caused a marked increase in ileal myeloperoxidase activity and conversion of the mucosa from an absorptive to a secretory state. TNBS-treated guinea pigs had a similar, marked increase in granulocyte infiltration and a mucosal secretory response. However, in contrast to naive animals,l-NAME treatment was anti-inflammatory, reverting all responses to the basal state. We conclude that intestinal nitric oxide serves an antiinflammatory role under basal conditions, whereas in the TNBS model of chronic ileitis, nitric oxide is a critical mediator of gut injury.