Nitric oxide: the Jekyll and Hyde of gut inflammation.
We studied the effects of seven day treatment with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NAME), administered in the drinking water (100 micrograms/ml ad 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 has 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 anti-inflammatory role under basal conditions, whereas in the TNBS model of chronic ileitis, nitric oxide is a critical mediator of gut injury.
Miller
M J
MJ
Department of Pediatrics, Louisiana State University School of Medicine, New Orleans 70112-2822.
Chotinaruemol
S
S
Sadowska-Krowicka
H
H
Kakkis
J L
JL
Munshi
U K
UK
Zhang
X J
XJ
Clark
D A
DA
D000284:Administration, Oral; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007079:Ileitis / Q000473:pathology / Q000503:physiopathology*; D007082:Ileum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009195:Peroxidase / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D009569:Nitric Oxide; D014302:Trinitrobenzenesulfonic Acid; D001120:Arginine; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester