Mechanisms underlying stimulation of gastroduodenal HCO3- secretion by NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, in rats.

Abstract

We investigated the mechanism underlying stimulation of HCO3- secretion by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the gastroduodenal mucosa of anesthetized rats. A chambered stomach (in the presence of omeprazole) or a duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 by a pH-stat method. Intravenous administration of L-NAME increased gastroduodenal HCO3- secretion with a concomitant rise in arterial blood pressure and a decrease in heart rate, and the changes were all antagonized by simultaneous administration of L-arginine. Vagotomy had no effect on the increased blood pressure response, but significantly inhibited the decrease of heart rate and increase of HCO3- secretion caused by L-NAME. The HCO3- stimulatory action of L-NAME was also inhibited by prior administration of yohimbine or prazosin. These agents alone lowered blood pressure and reduced the magnitude of the blood pressure response caused by L-NAME, leading to inhibition of heart rate changes. When delta HCO3- output induced by L-NAME was plotted against delta blood pressure change (from basal values) under various conditions, a significant relationship was found between these two factors. These results suggest that L-NAME stimulates gastroduodenal HCO3- secretion in association with the inhibition of endogenous NO production, and this mechanism may be in part mediated by a neural reflex through the vagal efferent nerve, resulting from the pressor response to L-NAME.