Cytoprotective action of L-arginine against HCl-induced gastric injury in rats: involvement of nitric oxide?

We examined the cytoprotective effect of L-arginine on gastric damage induced by 0.6 N HCl in rats and investigated whether the mechanism of this action is related to the nitric oxide (NO)-mediated protection. The animals were given 0.6 N HCl by gavage and killed 1 hr later. L-Arginine (100, 300 and 750 mg/kg) given p.o. 30 min before HCl treatment prevented these lesions in a dose-dependent manner, but had no effect when given i.v. (200 mg/kg). Similar effects were observed by D-arginine but not by an equimolar dose of mannitol. This effect of L-arginine (p.o.) was attenuated significantly by prior administration of indomethacin (5 mg/kg, s.c.) but not by NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg, i.v.), the NO synthase inhibitor. Both L- and D-arginine produced a reduction in potential difference (PD), inhibition of gastric motility, and increases of luminal pH and mucosal blood flow when they were given intragastrically. Indomethacin significantly mitigated these changes induced by L-arginine except PD reduction, while L-NAME showed significant inhibition only against the increased pH response. We conclude that L-arginine given p.o. exhibits gastric cytoprotection against HCl-induced damage in rats, probably by acting as a mild irritant. The mechanism of this action may appear through "adaptive cytoprotection" mediated by endogenous prostaglandins and does not involve the NO-mediated protective pathway.