Acute gastric lesions induced by the administration of histamine to rats with partial vascular occlusion: evidence for the gastroprotective effect of prostaglandin.
BACKGROUND
Histamine is not only a potent stimulator of gastric acid secretion, but it also plays a central role in gastroduodenal ulcerogenesis. In the present study we tested the effect of pre-treatment with exogenous prostaglandin E(2) (PGE(2)) in a new rat model of experimental gastric ulcers induced by combination of histamine and gastric ischemia.


METHODS
In male Wistar rats, a chronic ischemia of gastric mucosa was induced via the clamping of the left gastric artery and vein (L-AV) in combination with pylorus ligation. The following treatment groups of rats (6 rats/group) were investigated: 1) histamine alone (40 mg/kg twice s.c.); 2) vehicle (saline) followed 30 min later by gastric mucosal L-AV ischemia and pylorus ligation combined with histamine (40 mg/kg twice s.c.) and 3) PGE(2) (5 microg/kg i.g.) followed 30 min later by gastric mucosal L-AV ischemia combined with histamine (40 mg/kg twice s.c.) and pylorus ligation. At 4 hr after the clamping of L-AV and pylorus ligation, the area of gastric lesions and gastric acid secretion was determined.


RESULTS
Histamine treatment failed to produce gastric lesions, but when it was combined with ischemia, the widespread gastric lesions in the corpus mucosa, but not in the antrum, were observed. This damaging effect and decrease in the GBF were significantly attenuated by pretreatment with PGE(2).


CONCLUSIONS
The present study demonstrates that gastric hypersecretion induced by histamine in combination with gastric mucosal ischemia results in gastric lesions which progress into chronic gastric ulcers.
Konturek
P C
PC
Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany. peter.konturek@uk-erlangen.de
Brzozowski
T
T
Raithel
M
M
Sliwowski
Z
Z
Konturek
S J
SJ
Neurath
M F
MF
D000818:Animals; D000897:Anti-Ulcer Agents; D015232:Dinoprostone / Q000494:pharmacology*; D004195:Disease Models, Animal; D006632:Histamine; D007511:Ischemia / Q000473:pathology*; D008026:Ligation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D013270:Stomach / Q000098:blood supply*; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D006632:Histamine; D015232:Dinoprostone