Rat gastric injury after lipopolysaccharide: role of inducible nitric oxide synthase.
BACKGROUND
Short-term treatment with lipopolysaccharide (LPS) causes morphologic, but not macroscopic, gastric injury and decreases gastric injury caused by a subsequent challenge with a luminal irritant. This effect is abrogated by inducible nitric oxide synthase (iNOS) inhibition. The effects of long-term treatment with LPS on gastric injury are unknown as is the role of iNOS. We hypothesized that LPS would cause macroscopic gastric injury at later time points through an iNOS-dependent pathway.


METHODS
Conscious rats were given saline or LPS (1 or 20 mg/kg intraperitoneal) as a single intraperitoneal injection and killed 24 to 72 hours after injection. Macroscopic gastric injury (computerized planimetry), gastric luminal fluid volume and pH, and iNOS protein levels were assessed.


RESULTS
When compared with saline, high-dose but not low-dose LPS caused macroscopic gastric injury, increased gastric luminal fluid and pH, and up-regulated iNOS at 24 and 48 hours. All assessments returned to baseline by 72 hours. Inhibition of iNOS with 1400W (1 mg/kg intraperitoneal) given 15 minutes before saline or LPS (20 mg/kg) attenuated the deleterious effects of LPS on gastric injury and pH, but not fluid accumulation.


CONCLUSIONS
These data suggest that prolonged treatment with high-dose LPS causes gastric injury through an iNOS-mediated pathway.
Robinson
Emily K
EK
Department of Surgery, University of Texas Health Science Center, Houston, TX 77026, USA.
Kennison
Sasha D
SD
Suliburk
James W
JW
Mercer
David W
DW
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D007097:Imines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats
D007097:Imines; D008070:Lipopolysaccharides; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat