AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS: Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured by laser-Doppler flowmetry. RESULTS: ET-3 and an ET(B) receptor antagonist significantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Capsaicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. CONCLUSION: Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ET(B) receptor and by sensory afferent neurons.
AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS:Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured by laser-Doppler flowmetry. RESULTS: ET-3 and an ET(B) receptor antagonist significantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Capsaicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. CONCLUSION: Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ET(B) receptor and by sensory afferent neurons.
Authors: B D'Agostino; C Advenier; M Falciani; L Gallelli; G Marrocco; E Piegari; A Filippelli; F Rossi Journal: Br J Pharmacol Date: 2001-12 Impact factor: 8.739
Authors: F L David; A C I Montezano; N A Rebouças; D Nigro; Z B Fortes; M H C Carvalho; R C A Tostes Journal: Braz J Med Biol Res Date: 2002-09 Impact factor: 2.590
Authors: Paula R S Camara; Gerson J N Ferraz; Carla F Franco-Penteado; Lourenco Sbragia-Neto; Luciana R Meirelles; Simone A Teixeira; Marcelo N Muscara; Licio A Velloso; Edson Antunes; Jose G P Ferraz Journal: Eur J Pharmacol Date: 2008-05-16 Impact factor: 4.432