STIMULATION BY NITRIC-OXIDE SYNTHASE INHIBITORS OF GASTRIC AND DUODENAL HCO3- SECRETION IN RATS

The role of nitric oxide (NO) in the regulation Of gastroduodenal HCO3 - secretion was investigated in anesthetized rats using the NO biosynt hesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). HCO3- sec retion was measured at pH 7.0 using a pH-stat method in the chambered stomach in the presence of omeprazole or in the proximal duodenum. Int ravenous administration Of L-NAME (1-5 mg/kg) increased HCO3- secretio n in a dose-dependent manner in both the stomach and duodenum, with a concomitant elevation of arterial blood pressure. The stimulatory effe ct Of L-NAME on HCO3- secretion was mimicked by another NO synthase in hibitor, N(G)-monomethyl-L-arginine (50 mg/kg), but not by the enantio mer N(G)-nitro-D-arginine methyl ester, and was significantly antagoni zed by concurrent administration Of L-arginine, but not D-arginine, at 200 mg/kg. The exogenous NO donor nitroprusside (4 mg/kg) by itself d ecreased the rate of HCO3- secretion and significantly antagonized the HCO3- stimulatory action Of L-NAME. Furthermore, the increased HCO3- secretion caused by L-NAME was significantly attenuated by prior admin istration of atropine (1 mg/kg, s.c.) or indomethacin (5 mg/kg, s.c.) and by bilateral vagotomy but was not influenced by sensory deafferent ation after capsaicin pretreatment, though none of the treatments had any effect on the changes in blood pressure induced by L-NAME. These r esults suggest that L-NAME stimulates HCO3 Secretion in the gastroduod enal mucosa. This action is associated with the inhibition of NO biosy nthesis and may be partly dependent on vagal-cholinergic innervation a nd mediated by endogenous prostaglandins.