Effect of centrally administered losartan on gastric and duodenal ulcers in rats.
The effect of centrally administered losartan, an AT(1) receptor antagonist, on gastric acid secretion and gastric cytoprotection was studied using different models of gastric ulcers, such as acetic acid-induced chronic gastric ulcers, pylorus ligation, ethanol-induced and stress-induced acute gastric ulcers and cysteamine hydrochloride-induced duodenal ulcer. Losartan was administered intracerebroventrically (i.c.v.) at 2 different doses (125 and 250 microg/kg). Both doses of losartan increased the healing of acetic acid-induced chronic gastric ulcers. In pylorus-ligated rats, a significant reduction in free acidity, total acidity and ulcer index was observed with high dose (250 microg/kg, i.c.v.), while low dose (125 microg/kg, i.c.v.) produced reduction only in free acidity and ulcer index. Both doses also produced a significant antiulcer effect in ethanol-induced and stress-induced gastric ulcers. Losartan also reduced ulcer area in cysteamine-induced duodenal ulcer. We conclude that AT(1) receptor antagonism in the brain increases healing of gastric ulcers and reduces gastric acid secretion and increases gastric mucin content.
Merai
Ankitkumar Harshadrai
AH
Department of Pharmacology, Krupanidhi College of Pharmacy, Bangalore, India.
Asad
Mohammed
M
Prasad
V Satya
VS
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000188:drug therapy* / Q000503:physiopathology; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D005752:Gastric Mucins / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000503:physiopathology
D047228:Angiotensin II Type 1 Receptor Blockers; D000897:Anti-Ulcer Agents; D005752:Gastric Mucins; D019808:Losartan