The effects of verapamil on stress- and histamine-induced gastric lesions in rats.
The influence of verapamil on stress-induced and histamine-induced gastric ulcers was investigated in rats. The influence of verapamil was also examined on various biochemical parameters that affect the development of these ulcer models. The animals were pretreated with intraperitoneal verapamil (1, 5, 25 mg/kg) by injection 1 h before the induction of experimental ulceration. The gastric lesions were induced by cold-restraint stress or intraperitoneal injection of histamine (300 mg/kg). The gastroprotective effects of verapamil were evaluated by determining the ulcer index, gastric mucus content, free and total acidity, lipid peroxidation and non-protein sulfhydryl content. Verapamil pretreatment at a dose of 25 mg/kg significantly reduced stress-induced ulcers. Verapamil enhanced mucus secretion, reduced total acidity and lipid peroxidation and decreased non-protein sulfhydryl content in a dose-dependent fashion. On the other hand, pretreatment with verapamil at any dose had no significant effect on histamine-induced ulcers. L-Arginine (L-A) (100 mg/kg) or L-nitroarginine (L-NNA) (100 mg/kg) were also injected i.p. to the animals 1 h before stress to test the role of nitric oxide (NO) in the mechanism of the gastroprotective activity of verapamil (25 mg/kg). The results suggested that verapamil stimulates gastric NO production, but the overproduction of NO worsens gastric ulcers. The effects of verapamil on experimentally induced ulcers may be related to its ability to induce biochemical alterations in the parameters measured in gastric tissue.
Sirmagul
B
B
Osmangazi University, Medical School, Department of Pharmacology, Eskisehir, Turkey.
Kilic
F S
FS
Batu
O
O
Erol
K
K
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D005745:Gastric Acidity Determination; D005752:Gastric Mucins / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006632:Histamine / Q000008:administration & dosage / Q000009:adverse effects*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D019335:Nitroarginine / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D013276:Stomach Ulcer / Q000188:drug therapy / Q000209:etiology*; D013312:Stress, Physiological / Q000150:complications* / Q000503:physiopathology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use*
D005752:Gastric Mucins; D013438:Sulfhydryl Compounds; D019335:Nitroarginine; D006632:Histamine; D001120:Arginine; D014700:Verapamil