Effect of Centrally Administered Losartan on Gastric and Duodenal Ulcers in Rats

Abstract

The effect of centrally administered losartan, an AT₁ 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 μg/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 μg/kg, i.c.v.), while low dose (125 μg/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 AT₁ receptor antagonism in the brain increases healing of gastric ulcers and reduces gastric acid secretion and increases gastric mucin content.

RETRACTION: Role of Angiotensin-(1–7) in Gastroprotection against Stress-Induced Ulcerogenesis. The Involvement of Mas Receptor, Nitric Oxide, Prostaglandins, and Sensory Neuropeptides

“…However, the blockade of AT 1 receptors does not influence gastroprotective action of glucocorticoids released during stress (Filaretova et al, 1998;Pavel et al, 2008). Similarly, AT 1 -receptor antagonists dose-dependently attenuated gastric ulcers in rodents (Merai et al, 2009;Morsy et al, 2009) and counteracted the effects of ischemia and inflammation by the reduction in mucosal neutrophil infiltration and expression of gastric intercellular adhesion molecule 1 and TNF-a (Saavedra et al, 2005(Saavedra et al, , 2006. It is not excluded that the beneficial effect of AT 1 -receptor antagonists could depend on enhancement of the concentration of angiotensin metabolites Ang-(1-7) and Ang-(129) (Neves et al, 2000;Olszanecki et al, 2009), but this hypothesis requires further studies.…”

The renin–angiotensin system and the gastrointestinal mucosa

“…This mucosa protective effect has been proposed to be due to AT1 receptor mediated modulation of inflammatory factors, reduction of sympathetic neural activity and preservation of gastric mucosal blood perfusion (Pavel et al 2008). Reduced gastric acid and increased mucin secretions have been suggested to be other mechanisms of importance for attenuating experimental gastroduodenal ulcerations but the site of interference with the AT1 receptor is then in the CNS (Merai et al 2009). Indomethacin-induced rat small intestinal injuries have been reported to be prevented by the AT1 receptor antagonist CV-11974 .…”

Renin-Angiotensin System Associated with Risk of Upper GI Mucosal Injury Induced by Low Dose Aspirin

“…We also indicated the possible inverse association between peptic ulcer and angiotensin type 1 receptor (AT1R) blocker (ARB) or angiotensin I-converting enzyme (ACE) inhibitor, but not any other anti-hypertensive medicine such as Ca-blocker and a or ß-blocker among patients taking low-dose aspirin [6]. The previous experimental animal studies indicated that ARB or ACE inhibitor prevents stress-induced peptic ulcers [7][8][9][10][11][12][13]. However, only our recent clinical study indicated inverse association of ARB or ACE inhibitor with aspirin induced peptic ulcer [6], and clinical data are still lacking.…”