Effects of cimetidine upon gastric secretion and mucosal blood flow in the rat stressed by restraint. A dose-response and prophylaxis trial.

Abstract

The effect of the histamine-H2-receptor blocking agent cimetidine (CT) on gastric secretion, mucosal blood flow (MBF), and gastric mucosal stress ulcer index was studied in rats (n = 96) during control conditions (3.9, 15.6, 62.4 microMol/kg/h CT i.p. over 8 h) with calculation of kinetic constants (Vmax; Km) for gastric secretion, MBF and ulcer index, it is shown that CT actions become considerably modified by severe stress. Under mild stress the reduction of MBF and acid secretion by increasing CT doses is parallel. Severe stress alone reduces MBF more than gastric acid (65 vs. 30%). This phenomenon is partly reversed by a dose of 62.4 microMol/kg/h (= 16 mg/kg/h), which is associated with the lowest ulcer index observed. There is no significant correlation between the latter and either acid concentration, acid output, or MBF. The concentrations of pepsin in gastric juice or of serum gastrin neither change with severe stress alone or with additional CT. It is concluded that CT has anti-stress ulcer properties coinciding with reduced acidity in the gastric lumen, but that in addition this beneficial effect may be mediated by factors other than acid reduction.