Histamine in stress ulcer prophylaxis in rats.
BACKGROUND
Gastrin and its analogues increase the gastric acid secretion, but also enhance mucosal defense mechanisms. On the other hand, increased formation of histamine leading to an increase in gastric acid secretion is accompanied with gastroprotection and acceleration of gastric ulcer healing.


OBJECTIVE
Of this study was to examine the effect of histamine on stress induced gastric ulcers in rats.


METHODS
Male Wistar rats were exposed to water immersion and restrain stress (WRS) for 3.5 h at 23 degrees C. Before WRS rats were pretreated with saline, histamine, ranitidine or omeprazole.


RESULTS
WRS produces gastric lesions which were strongly reduced by ranitidine or omeprazole. Also treatment with histamine markedly reduced ulcer area evoked by WRS. Addition of histamine to ranitidine or omeprazole caused an additional reduction in ulcer area. Gastroprotective effect of histamine was accompanied with the increase in gastric blood flow (GBF). Administration of omeprazole or ranitidine alone was without significant effect on GBF. Histamine caused an slight decrease in gastric luminal pH, whereas ranitidine or omeprazole significantly increased gastric luminal pH. Plasma interleukin-1beta was significantly reduced after administration of omeprazole, ranitidine, or histamine, however, the effect of histamine was less pronounced. DNA synthesis was increased after administration of omeprazole, ranitidine or histamine when compared with WRS alone. Administration of histamine in combination with ranitidine or omeprazole caused an additional increase in DNA synthesis.


CONCLUSIONS
Histamine exhibits protective effect and increases gastroprotective effect of ranitidine and omeprazole against stress-induced gastric lesions. This effect of histamine seems to be independent on gastric acid secretion but related to the increase in gastric blood flow and the reduction in activation of cytokine cascade.
Warzecha
Z
Z
Department of Physiology, Jagiellonian University Medical School, Kraków, Poland.
Dembiński
A
A
Brzozowski
T
T
Ceranowicz
P
P
Dembiński
M
M
Stachura
J
J
Konturek
S J
SJ
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000473:pathology; D005755:Gastrins / Q000097:blood; D006632:Histamine / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications*
D005755:Gastrins; D007375:Interleukin-1; D020011:Protective Agents; D006632:Histamine; D004247:DNA