ROLE OF NITRIC-OXIDE AND PROSTAGLANDINS IN GASTROPROTECTION INDUCED BY CAPSAICIN AND PAPAVERINE

Capsaicin and papaverine are potent vasorelaxants with strong gastropr otective activity against damage induced by absolute ethanol. This pro tection was originally attributed to the increase in gastric mucosal b lood flow (GBF) and the present study was designed to determine the po ssible role of nitric oxide (NO) and prostaglandins (PG) in the protec tive 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 are a of ethanol-induced lesions, the ED50 being 0.3 and 1 mg/kg, respecti vely. This protection was accompanied by a gradual increase in the GBF . Intravenous injection of N(omega)-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 prot ective and hyperemic effects of capsaicin and papaverine against ethan ol-induced damage and attenuated the increase in GBF induced by each o f these agents alone. This deleterious effect of L-NNA on the gastric mucosa and the GBF was fully antagonized by L-arginine (200 mg/kg i.v. ) but not by D-arginine. L-arginine partly restored the decrease in GB F induced by L-NNA. Pretreatment with indomethacin (5 mg/kg i.p.), whi ch suppressed the generation of PG by 85%, slightly enhanced the mucos al lesions induced by ethanol but failed to affect the fall in GBF ind uced by this irritant. Gastroprotective and hyperemic effects of capsa icin and papaverine were partly reversed by indomethacin suggesting th at endogenous PG are also implicated in these effects. Addition of L-N NA to indomethacin completely eliminated both the protective and hyper emic effects of capsaicin and papaverine. We conclude that both NO and PG contribute to the gastroprotective and hyperemic effects of capsai cin and papaverine on the gastric mucosa.