Efeito gastroprotetor do Sildenafil (Viagra®) na lesão gástrica induzida por álcool em ratos: papel do óxido nítrico, do GMPc e dos canais de potássio sensíveis ao ATP

Abstract

Recently, we demonstrated that sildenafil has protective effects against NSAID- induced gastric damage in rats, by a decrease in leukocytes adherence and increase in gastric blood flow (Santos CL et al, BJP, 2005). Ethanol induced gastric hemorrhagic damage in rats, by an increase in free radical production and decrease in mucosal glutathione concentration. AIMS: Aim of was work is to investigate if sildenafil has a protective effect against ethanol- induced gastric damage and the role of the way NO/cGMP/KATP in this event. METHODS: Sildenafil (0.1, 0.3, 1, or 3 mg/Kg, p.o) was administrated 30 min before ethanol 100% (4 ml/Kg, p.o). After 1 hour, rats were sacrificed and the stomachs opened along the greater curvature and the mucosal lesion area was measured by computer planimetry program. Furthermore, pieces of gastric mucosal were removed for microscopic analysis and glutathione measure, and hemoglobin concentrations (colorimetric test Bioclin). Other groups had been dealt with L-NAME (1 or 3 mg/kg, i.p), L-NAME (3 mg/kg, i.p) + L- Arg (200mg/kg, i.p), ODQ (10 mg/Kg, p.o), glibenclamide (0.1, 0.3, 1 ou 3 mg/Kg, p.o), glibenclamide (1 mg/Kg) + diazóxide (3mg/Kg, i.p) ou saline. After 30 min the rats had received sildenafil (1mg/kg), and after more 30 min ethanol 100% (4ml/kg, p.o), with the sacrifice occurring 1 h later. RESULTS: Absolute ethanol induced gastric damage (158.9 ± 9.3 mm2), and gastric mucosal hemorrhage (3787.0 ± 512.9 µg/100mg) and reduced gastric glutathione concentration (78.7 ± 9.5 µg/g). Sildenafil protected, in a dose dependent manner, the ethanol- induced gastric damage , with the maximum effect in the dose of 1 mg/Kg (44.5 ± 7.7 mm2). Sildenafil also reversed the decreased in gastric glutathione (143.6 ± 15.7 µg/g) induced by ethanol. Alone L-NAME (151.1 ± 20.9 mm2), ODQ (137.9 ± 41.6 mm2) and glibenclamide alone (137.1 ± 16,7 mm2) reverted the protection of the sildenafil. But, in the animals trated with L-NAME + L-arginine (30.9 ± 10.5 mm2), or glibenclamide + diazóxido (60.3 ± 2.0 mm2) did not have changes in the effect of the sildenafil. CONCLUSION: Sildenafil had a gastric protective effect against ethanol- induced gastric damage through the activation of the NO/cGMP/KATP pathway, at least in part through a increase in stomach GSH.