The influence of cimetidine, a histamine H2-receptor antagonist, on the gastric effects of reserpine in rats.
The effects of graded doses of cimetidine on both resting and reserpine-evoked gastric acid secretion were examined in relation to their influence on reserpine-induced ulceration, mast cell degranulation and mucosal microcirculatory changes in rat stomachs. Cimetidine 10 mg/kg or above reduced resting or reserpine-provoked gastric acid secretion as well as rumenal and glandular ulceration. However, non-acid-inhibiting doses, 5 mg/kg or below, continued to prevent glandular ulceration. Reserpine-evoked gastric glandular mucosal mast cell degranulation was unaffected by both acid-inhibiting and non-acid-inhibiting doses of cimetidine which dose-dependently blocked the superficial glandular mucosal microcirculatory volume changes. These results suggest that cimetidine prevents reserpine-induced glandular ulceration largely by blocking the ulcerogenic effect of histamine H2-receptor-mediated mucosal microcirculatory congestion, in contrast to antagonising rumenal lesions through acid inhibition; they also support the idea tha reserpine may release histamine mainly from the glandular mucosal mast cells. The possibility of another antiulcer mechanism, due to cytoprotection, is discussed.
D000818:Animals; D002452:Cell Count; D002927:Cimetidine / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects; D008833:Microcirculation; D051381:Rats; D012110:Reserpine / Q000009:adverse effects*; D013270:Stomach / Q000166:cytology / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced
D006146:Guanidines; D002927:Cimetidine; D012110:Reserpine