Effects of cimetidine upon gastric secretion and mucosal blood flow in the rat stressed by restraint

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.

Increase in Lipid Peroxidation in Rat Gastric Mucosal Lesions Induced by Water-Immersion Restraint Stress

“…Key Words: gastric mucosal lesions, lipid peroxidation, microcirculation, thiobarbituric acid-reactive substances, water-immersed restraint stress Several pathogenetic mechanisms have been suggested to account for stressinduced gastric mucosal lesions: disturbance of gastric mucosal microcirculation [1][2][3][4][5], alteration in gastric secretion [2,6], abnormal gastric motility [7], and hyperacidity [6].…”

Protective effect of chemical stimulation of cerebellar fastigial nucleus on stress gastric mucosal injury in rats

“…In recent years, much data has indicated that the mechanisms of SGMI have been implicated in the pathogenesis of increase in gastric acid and pepsin secretion, a decrease in gastric mucosal blood flow, inhibition of endogenous generation of prostaglandins, increased generation of reactive oxygen species, suppression of gastric mucosal cell growth and proliferation (Das and Banerjee, 1993;Hemmer et al, 1980;Konturek et al, 1990). However, little is known about the role of the central nuclei in regulating SGMI.…”

Endoplasmic reticulum stress response is involved in the pathogenesis of stress induced gastric lesions in rats

“…At present, the cellular and molecular mechanisms involved in gastric mucosal defense against gastrodamaging factors are well known (Wallace and Granger, 1996). Several aggressive mechanisms have been implicated in the pathogenesis of stress ulcers, including increased secretion of gastric acid and pepsin and increased generation of reactive oxygen species (Das and Banerjee, 1993;Hemmer et al, 1980;Konturek et al, 1990). However, the mechanisms underlying the mucosal damage mediated by aggressive factors remain elusive.…”