Background and purpose:
Sildenafil is a selective inhibitor of cGMP‐specific phosphodiesterase. Sildenafil, acting via NO‐dependent mechanisms, prevents indomethacin‐induced gastropathy. Activation of ATP‐sensitive potassium channels (KATP) is involved in gastric defence. Our objective was to evaluate the role of the NO/cGMP/KATP pathway in the protective effects of sildenafil against ethanol‐induced gastric damage.
Experimental approach:
Rats were treated with L‐NAME (1 or 3 mg kg−1, i.p.) or with L‐arginine (200 mg kg−1, i.p.) +L‐NAME (3 mg kg−1, i.p.), the guanylate cyclase inhibitor, ODQ (10 mg kg−1, i.p.), glibenclamide (0.1, 0.3, 1 or 3 mg kg−1, i.p.) or with glibenclamide (1 mg kg−1, i.p.) + diazoxide (3 mg kg−1, i.p.). After thirty minutes, the rats received sildenafil (1 mg kg−1, by gavage), followed by intragastric instillation of absolute ethanol (4 ml kg−1) to induce gastric damage. One hour later, gastric damage (haemorrhagic or ulcerative lesions) was measured with a planimetry programme. Samples of stomach were also taken for histopathological assessment and for assays of tissue glutathione and haemoglobin.
Key results:
Sildenafil significantly reduced ethanol‐induced gastric damage in rats. L‐NAME alone, without L‐arginine, significantly reversed the protection afforded by sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the gastric protective effect of sildenafil against ethanol‐induced gastric damage. Glibenclamide alone reversed sildenafil's gastric protective effect. However, glibenclamide plus diazoxide did not alter the effects of sildenafil.
Conclusions:
Sildenafil had a protective effect against ethanol‐induced gastric damage through the activation of the NO/cGMP/KATP pathway.
British Journal of Pharmacology (2008) 153, 721–727; doi:; published online 10 December 2007
RESUMOgástrico (GAVE). No presente trabalho, relatamos o caso de uma paciente de 52 anos, com cirrose hepática e ectasia vascular do antro gástrico, que apresentou seis episódios de hemorragia digestiva alta com necessidade de transfusão sanguínea, apesar da terapia endoscópica estabelecida. Iniciamos talidomida na dose de 100 mg/dia que em seguida foi reduzida para 50 mg/dia. transfusões sanguíneas. Apesar da interrupção da terapêutica endoscópica, persistiu assintomática e a endoscopia de controle após 3 meses não visualizava mais sangramento ativo nas lesões do antro. Portanto, este trabalho tem como objetivo descrever que a Palavras-chave: Talidomida. Sangramento. Ectasia vascular do antro gástrico. Coagulação com plasma de argônio.
ABSTRACT
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