Acid-Inhibitory Potency of Ranitidine in Diabetic Rats

Abstract

The pharmacological potency of ranitidine to inhibit pentagastrin-stimulated gastric acid outputs was studied in early diabetic rats. Diabetes was induced by intravenous injection of streptozotocin 4 days before the acid study. The gastric acid output was measured every 5 min by automatic titration of collected gastric perfusates. Basal acid was collected for 45 min before a 90-min infusion of pentagastrin. Thirty minutes after onset of the pentagastrin infusion, the rats received intravenous bolus injections of ranitidine at doses of 0.03, 0.3, or 3 mg/kg. Diabetes induction obviously increased the acid-secretory ability during the pentagastrin stimulation period. Ranitidine given at the low dose to diabetic rats showed no apparent inhibitory potency (mean ± SE 106 ± 3.4 vs. 63.9 ± 3.3%, p < 0.01) with shorter duration (21.3 ± 5.4 vs. 44.4 ± 7.9 min, p < 0.05) of inhibited acid output as compared with controls. The median dose of ranitidine treatment produced less effect of an acid-inhibitory potency in diabetic rats (p < 0.05). Among the rats which received the high dose of ranitidine, the inhibitory action on the acid secretion remained diminished in diabetic rats (39.3 ± 2.1 vs. 55.1 ± 4.2%, p < 0.05). In conclusion, short-term diabetes induction in rats enhances their stimulatory acid output ability, but attenuates the pharmacologically inhibitory action of ranitidine on the stimulated acid output.