Acid-inhibitory potency of ranitidine in diabetic rats.
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.
Chang
Full-Young
FY
Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan. changfy@vghtpe.gov.tw
Chen
Tseng-Shing
TS
Lee
Shou-Dong
SD
Yeh
Guey-Hwa
GH
Doong
Ming-Luen
ML
Wang
Paulus S
PS
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013997:Time Factors
D001786:Blood Glucose; D006635:Histamine H2 Antagonists; D013311:Streptozocin; D011899:Ranitidine; D010418:Pentagastrin