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 body-weight (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 (rs > or = 0.3, P = 0.04). L-NAME l 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.
Neilly
P J
PJ
Department of Surgery, Queen's University of Belfast, UK.
Kirk
S J
SJ
Gardiner
K R
KR
Anderson
N H
NH
Rowlands
B J
BJ
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D005260:Female; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
D009569:Nitric Oxide; D014302:Trinitrobenzenesulfonic Acid; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester