The mechanism underlying stimulation of gastric HCO 3 − secretion by the nitric oxide synthase inhibitor N g ‐nitro‐ l ‐arginine methyl ester in rats

We investigated the mechanism underlying stimulation of gastric HCO 3 − secretion by the nitric oxide (NO) synthase inhibitor N g ‐nitro‐ l ‐arginine methyl ester ( l ‐Name) in anaesthetized rats. A rat stomach was mounted in an ex vivo chamber, superfused with saline, and HCO 3 − secretion was measured in the absence of acid secretion (omeprazole pretreatment). Intravenous administration of l ‐Name (1‐5 mg/kg) increased gastric HCO 3 − secretion dose dependently with concomitant rise in arterial blood pressure and decrease in heart rate, and these effects were all antagonized by simultaneous administration of l ‐arginine (200 mg/kg). Vagotomy did not affect the increased blood pressure response but significantly inhibited the decrease in heart rate and increase of HCO 3 − secretion caused by l ‐Name. The HCO 3 − stimulatory action of l ‐Name was also inhibited by pretreatment with either yohimbine (5 mg/kg s.c.) or prazosin (0.5 mg/kg s.c.). These agents alone caused a decrease in blood pressure, and reduced the magnitude of blood pressure response caused by l ‐Name, leading to inhibition of heart rate changes. When the change in HCO 3 − output induced by l ‐Name was plotted against the change in blood pressure (from basal values) under various conditions, a significant relationship was found between these two parameters. These results suggest that l ‐Name stimulates gastric HCO 3 − secretion in association with the inhibition of endogenous NO production, and this mechanism may be in part mediated by a neural reflex through vagal efferent nerves, resulting from the pressor response to l ‐Name.