DELAYED GASTRIC-EMPTYING INDUCED BY INHIBITORS OF NITRIC-OXIDE SYNTHASE IN RATS

The effect of the nitric oxide (NO) synthase inhibitor, N-G-nitro-L-arginine methyl ester, on gastric emptying of a non-nutrient solution was investigated in conscious rats. N-G-Monomethyl-L-arginine (10 mg/kg i.v.) and N-G-nitro-L-arginine methyl ester (3 or 10 mg/kg i.v.) inhibited the 20-min rate of gastric emptying of liquids by 34%, 69% and 84% respectively, whereas the 0.3 mg/kg of N-G-nitro-L-arginine methyl ester or 3 mg/kg of N-G-monomethyl-L-arginine had no effect. The inhibitory effect of N-G-nitro-L-arginine methyl ester (3 mg/kg) was prevented by L-arginine (300 mg/kg i.v.), but not by D-arginine (300 mg/kg i.v.). N-G-Nitro-L-arginine methyl ester (0.3-10 mg/kg) induced a dose-related increase in mean blood pressure up to 161+/-10 mm Hg. Spontaneous hypertensive rats with a mean blood pressure of 180+/-5 mm Hg had a gastric emptying rate of 51.9+/-6.1%. These data indicate that NO synthase inhibitors given i.v. at doses that inhibit NO synthase, delay gastric emptying through mechanisms which are unrelated to changes in arterial blood pressure.