Investigation of the mechanisms underlying the gastroprotective effect of nicorandil.
OBJECTIVE
This study investigated possible mechanisms underlying the gastroprotective effect of nicorandil on experimentally-induced gastric lesions in rats.


METHODS
Rats were randomly assigned to vehicle-, nicorandil (10 mg/kg)-, glibenclamide (6 mg/kg)-, nicorandil + glibenclamide- and cimetidine-pretreated groups, in addition to non-stressed control group, to demonstrate whether the K(ATP )channel opening contributed to nicorandil's gastroprotection. Lesions were induced by water immersion-restraint stress (WIRS) and ulcer indices were determined. Gastric juice parameters (pH, acid output, pepsin and mucin concentrations) were determined. Another set of rats was divided into control, saline-pretreated and nicorandil (10 mg/kg)-pretreated groups. Rats underwent WIRS and their stomachs were used for determination of gastric mucosal lipid peroxides, histamine, PGE(2), and total nitrites levels.


RESULTS
Nicorandil displayed significant protection against gastric lesions formation, abolished by concomitant administration of glibenclamide. Nicorandil significantly reduced gastric acid and pepsin secretion, but upon coadministration with glibenclamide, these effects were blocked. Additionally, nicorandil significantly reduced gastric mucosal lipid peroxides and total nitrites, but did not affect PGE(2) and histamine levels.


CONCLUSIONS
Results confirm a gastroprotective effect for nicorandil, the mechanism of which comprises K(ATP) channel opening, free radical scavenging, decrease of pepsin and acid secretion and prevention of the detrimental rise in nitric oxide during WIRS.
Ismail
H A F
HA
Department of Pharmacology and Toxicology, Faculty of Pharmacy, El-Minia University, El-Minia, Egypt. hafmael@yahoo.com
Khalifa
M M A
MM
Hassan
M K
MK
Ashour
O M
OM
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002927:Cimetidine / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005750:Gastric Juice / Q000737:chemistry; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D007101:Immersion; D008297:Male; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels / Q000819:agonists*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications
D000897:Anti-Ulcer Agents; D015221:Potassium Channels; D020108:Nicorandil; D002927:Cimetidine; D005905:Glyburide