MANIPULATION OF THE L-ARGININE NITRIC-OXIDE PATHWAY IN EXPERIMENTAL COLITIS

The role of the L-arginine-nitric oxide pathway in the pathogenesis of colonic inflammation was assessed using L-arginine and its competitive analogue N-omega-nitro-L-arginine methyl ester (L-NAME) in a rat model of colitis. In the first study oral L-arginine 2 per cent (control: 3.4 per cent L-glycine) was administered with and without L-NAME 100 mg/l. Orally administered L-arginine increased colonic inflammation (P=0.004) and decreased thymic weight (P=0.0007). Addition of L-NAME reduced the colonic inflammation and prevented loss of bodyweight (P<0.04). In the second study L-NAME was administered orally in concentrations of 100, 200 and 500 mg/l (control: no L-NAME). L-NAME 500 mg/l reduced colonic inflammation and increased thymic weight and body-weight (P<0.01). Thymic weight and body-weight correlated positively with the concentration of L-NAME administered orally (r(s) greater than or equal to 0.3, P=0.04). L-NAME I g/l was administered topically as an enema (control: suspension agent). Topical L-NAME reduced colonic inflammation and increased thymic weight (P<0.05). These results suggest that the L-arginine-nitric oxide pathway mediates colonic inflammation in this model.