Mechanisms Underlying Stimulation of Gastroduodenal HCO3_ Secretion by N-Nitro-L-Arginine Methyl Ester, an Inhibitor of Nitric Oxide Synthase, in Rats

Abstract

ABSTRACT-We investigated the mechanism underlying stimulation of HC03 secretion by the nitric ox ide (NO) synthase inhibitor 1V°-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 HC03 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 HC03_ secretion caused by L-NAME. The HC03 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 JHC03_ output induced by L-NAME was plotted against dblood 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 HC03_ 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.

Stimulation of duodenal HCO3− secretion by hydrogen sulphide in rats: relation to prostaglandins, nitric oxide and sensory neurones

“…30 min before NaHS. Although l ‐NAME was reported to increase duodenal HCO 3 − secretion mediated by a neuronal reflex due to a marked elevation of arterial blood pressure, this response was observed acutely for about 2 h and returned to basal levels within 3 h (Takeuchi et al. 1993, 1994, Sugamoto et al.…”

Role of Nitric Oxide in Mucosal Blood Flow Response and the Healing of HCI-lnduced Lesions in the Rat Stomach

“…We previously reported that acid secretion was decreased in the stomach following injury, mediated at least partly by endogenous NO, and L-NAME significant ly restored the acid response in the damaged stomach, although this agent had no effect on basal and histaminestimulated acid secretion in the intact stomach [10,26], It is possible that the inhibition of NO production by L-NAME sustained acid secretion by suppressing the NOmediated inhibitory pathway in the stomach following damage by HCI. In addition, L-NAME alone in the nor mal stomach has no effect on mucosal blood flow and mucosal vascular permeability, and does not cause any macroscopic damage in the mucosa [27,28], although the data on basal mucosal blood flow are not without contro versy among investigators; a decrease or no change has been reported, depending on the experimental conditions [27,29,30]. Thus it is unlikely that inhibition of NO pro duction by L-NAME causes a reduction of basal mucosal blood flow and such a reduction alone could affect the healing of acute gastric lesions.…”