Effect of pibutidine hydrochloride on nitric oxide production in rat gastric mucosa

This study examined the effect of pibutidine hydrochloride, a novel histamine H2 receptor antagonist (IT-066), on nitric oxide (NO) production in gastric mucosa by measuring nitrite and nitrate contents. IT-066 (0.3-3 mg/kg, p.o.) and NO donors, sodium nitroprusside (0.3 mg/kg, s.c.) and NOR3 (0.1 mg/kg, s.c.), increased the NO contents in gastric mucosa. Cimetidine (100 mg/kg, p.o.), ranitidine (30 mg/kg, p.o.) and famotidine (10 mg/kg, p.o.) did not significantly affect the NO production. Pretreatment with NG-nitro-L-arginine methyl ester (3 mg/kg, i.v.), a NO synthase inhibitor, decreased the level of IT-066 (3 mg/kg, p.o.)-stimulated NO production. These results suggest that IT-066 stimulated gastric mucosal NO production, and that endogenous NO may be implicated in the pharmacological effect of IT-066.