The mechanism underlying stimulation of gastric HCO3- secretion by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester in rats.

Abstract

We investigated the mechanism underlying stimulation of gastric HCO3- secretion by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in anaesthetized rats. A rat stomach was mounted in an ex vivo chamber, superfused with saline, and HCO3- secretion was measured in the absence of acid secretion (omeprazole pretreatment). Intravenous administration of L-NAME (1-5 mg/kg) increased gastric HCO3- 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 HCO3- secretion caused by L-NAME. The HCO3- 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 HCO3- 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 HCO3- 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.