Indomethacin potentiates endotoxin-induced blood flow reduction and histological injury in rat gastric mucosa.
1. The effect of the intravenous administration of lipopolysaccharide from Salmonella typhosa endotoxin on arterial blood pressure (BP), gastric mucosal blood flow (GMBF) and gastric damage was studied in anaesthetized rats. The effect of the inhibition of endogenous prostaglandin generation by indomethacin on these parameters was also investigated in this model of endotoxin shock. 2. A similar and dose-dependent percentage of reduction in BP and GMBF was observed 5 min after a bolus injection of 20 or 30 mg kg-1 endotoxin. A transient recovery in GMBF at 15 min was observed followed by a second fall at 30 min, at a time when BP was slowly increasing. 3. Pretreatment with indomethacin (5 mg kg-1, s.c.) one hour before the administration of 30 mg kg-1 endotoxin, significantly augmented the reduction in GMBF without affecting the reduction in BP. 4. The gastric damage, assessed histologically, was similar and confined to the superficial mucosa 30 min after the administration of 20 or 30 mg kg-1 endotoxin. The histologically-assessed damage was significantly greater in indomethacin pretreated rats injected with 30 mg kg-1 endotoxin. 5. These findings suggest that endogenous prostaglandin generation plays a protective role in endotoxin-induced gastric mucosal microcirculatory disturbances and mucosal damage.
Piqué
J M
JM
West Los Angeles, VA Medical Center, California.
Yonei
Y
Y
Whittle
B J
BJ
Leung
F W
FW
Guth
P H
PH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004731:Endotoxins / Q000633:toxicity*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012485:Salmonella typhi; D012772:Shock, Septic / Q000503:physiopathology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000503:physiopathology
D004731:Endotoxins; D007213:Indomethacin