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Capsaicin and papaverine are potent vasorelaxants with strong gastroprotective activity against damage induced by absolute ethanol. This protection was originally attributed to the increase in gastric mucosal blood flow (GBF) and the present study was designed to determine the possible role of nitric oxide (NO) and prostaglandins (PG) in the protective and hyperemic effects of capsaicin and papaverine on rat gastric mucosa. We found that the pretreatment with capsaicin (0.1-0.5 mg/kg i.g.) or papaverine (0.1-2 mg/kg i.g.) reduced dose dependently the area of ethanol-induced lesions, the ED₅₀ being 0.3 and 1 mg/kg, respectively. This protection was accompanied by a gradual increase in the GBF. Intravenous injection of N^ω-nitro-L-arginine (L -NNA; 1.2-5 mg/kg), a selective blocker of NO synthase, which by itself caused only a small increase in ethanol lesions, reversed dose dependently the protective and …