Felodipine- and ethanol-induced gastric mucosal damage in rats.
Calcium channel blockers like verapamil have been shown to potentiate ethanol-induced gastric mucosal damage. However, the exact mechanism for this adverse drug interaction is still unknown. We used felodipine to study the ulcerogenic mechanisms of calcium channel blockers and the pathogenesis of ethanol-induced ulceration. The experiment was conducted in an ex vivo gastric chamber prepared in anesthetized animals. Felodipine (0.25, 0.5, 1.0, or 2.0 mg/kg s.c.) dose-dependently reduced the systemic blood pressure which was accompanied by a decrease in gastric mucosal blood flow (GMBF), with an insignificant change in heart rate. Ethanol lowered the GMBF and produced gastric mucosal lesions, and these actions were potentiated by felodipine. Preincubation with calcium gluconate but not the sodium salt attenuated the adverse effects of ethanol on GMBF and lesion formation; it also significantly prevented the gastric effects of felodipine but not the decrease of the systemic blood pressure. It is concluded that felodipine aggravates ethanol ulceration through a depressive action on the GMBF. These actions were attenuated by the supplementation with calcium ions in the gastric mucosa. Therefore, maintenance of calcium homeostasis in the gastric wall could play a significant role in the prevention of ethanol ulceration in rats.
Liu
X G
XG
Department of Gastroenterology, Medical University, Beijing, People's Republic of China.
Cho
C H
CH
Ko
J K
JK
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000633:toxicity*; D002125:Calcium Gluconate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D015736:Felodipine / Q000008:administration & dosage / Q000633:toxicity*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
D002121:Calcium Channel Blockers; D000431:Ethanol; D015736:Felodipine; D002125:Calcium Gluconate