Potassium channel modulators and indomethacin-induced gastric ulceration in rats.
BACKGROUND
Different mechanisms have been proposed for the pathophysiology of indomethacin-induced gastric ulceration (IIGU), including changes in gastric mucosal blood flow, motility, and acidity. It seems probable that adenosine 5'-triphosphate (ATP)-dependent potassium channels (K(ATP)) have a regulatory effect on the above factors. The aim of the present study was to investigate the effects of K(ATP) channel modulators, diazoxide as a channel opener and glibenclamide as a K(ATP) antagonist, on IIGU.


METHODS
Male rats were starved for 24 h. Groups of 10 animals were used. Diazoxide at doses of 5, 15, and 45 mg/kg and glibenclamide at doses of 2, 6, and 18 mg/kg were injected intraperitoneally 30 min before the subcutaneous injection of 30 mg/kg of indomethacin. To assess the effects of indomethacin on the gastric mucosal vascular bed, different doses of enalapril and hydralazine, two vasodilators with mechanisms of action independent of K(ATP), were also studied. Gastric mucosal ulceration was noted, and fasting blood sugar was assayed. The data were compared between the groups.


RESULTS
Indomethacin produced gastric ulceration in 100% of rats with a severity rating of 2.15/10. This was prevented by diazoxide and aggravated by glibenclamide. Diazoxide increased and glibenclamide decreased fasting blood sugar. Neither enalapril nor hydralazine showed any effect on IIGU and/or fasting blood sugar.


CONCLUSIONS
K(ATP) modulators may play an important role in the pathophysiology of IIGU through a peripheral action on mucosal and submucosal blood flow of the stomach, gastric motility, acidity, or an action on the vagus complex center of the brain.
Toroudi
H P
HP
Dept. of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Iran.
Rahgozar
M
M
Bakhtiarian
A
A
Djahanguiri
B
B
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D003981:Diazoxide / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D005905:Glyburide / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D007213:Indomethacin / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000503:physiopathology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; D006830:Hydralazine; D004656:Enalapril; D003981:Diazoxide; D005905:Glyburide; D007213:Indomethacin