Acid‐induced increase in duodenal mucosal alkaline secretion in the rat involves the L‐arginine/NO pathway

Abstract

Duodenal mucosal alkaline secretion increases in response to hydrochloric acid exposure. The tentative role of nitric oxide (NO) in the mediation of this response was investigated. The mucosal alkaline output by a duodenal segment was recorded by in situ titration in chloralose-anaesthetized rats. In some experiments the duodenal blood flow was estimated by laser-Doppler flowmetry. Exposure of the duodenum to acid (0.01 M HCl, 5 min) increased the alkaline secretion by approximately 85%. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1 intravenously or 0.3 mM intraluminally) blocked the secretory increment after mucosal acid exposure. Mean arterial pressure and basal alkaline secretion were markedly raised, whereas duodenal blood flow was decreased, when L-NAME was given intravenously (i.v.). Intraluminal (i.l.) administration left mean arterial pressure as well as duodenal blood flow unaltered, and the duodenal mucosal alkaline secretion was only slightly elevated. The stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) had no effect on either basal or acid-induced duodenal alkaline output. In animals receiving L-arginine (10 mg kg-1 min-1 i.v., or 3 mM i.l.) and L-NAME, the acid exposure elicited an increase in duodenal mucosal alkaline secretion, similar to that observed in controls. The results suggest that the acid-induced increase in duodenal mucosal alkaline secretion involves NO synthesis, which takes place close to the lumen, probably within the mucosa.

The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion

“…Intravenously administered L-NAME is therefore unsuitable, in our model, as a tool to elucidate the current discrete mechanisms influencing epithelial duodenal mucosal alkaline secretion, since the basal secretory levels will nearly overcome the upper limit for measurement of alkaline secretion. In the present study we found that intraluminally administered L-NAME, at a dose that blocks acid-induced alkaline secretion [18], did not inhibit CGP42112A induced secretion. It may be that the AT2-receptor-stimulated duodenal alkaline secretory response has a different pathway of mediation than the NO-dependent secretion that is induced by luminal acid.…”

“…We have previously shown that duodenal mucosal alkaline secretion elicited by infusion of CGP 42112A at the dose 0.1 μg kg -1 min -1 can be blocked by PD 123319 [3] and is therefore considered to be an AT2 receptor mediated process. We have also demonstrated that mucosal acid exposure is dependent on villus epithelial NO production and can be blocked by intraluminal administration of L-NAME [9,18,19]. It should be noted that systemic administration of L-NAME elicits an upward shift of the basal duodenal mucosal alkaline secretion in the rat [18,20] reflecting other points of action for the compound and making it difficult to interpret additional effects on the secretion by other interferences.…”

“…We have also demonstrated that mucosal acid exposure is dependent on villus epithelial NO production and can be blocked by intraluminal administration of L-NAME [9,18,19]. It should be noted that systemic administration of L-NAME elicits an upward shift of the basal duodenal mucosal alkaline secretion in the rat [18,20] reflecting other points of action for the compound and making it difficult to interpret additional effects on the secretion by other interferences. Intravenously administered L-NAME is therefore unsuitable, in our model, as a tool to elucidate the current discrete mechanisms influencing epithelial duodenal mucosal alkaline secretion, since the basal secretory levels will nearly overcome the upper limit for measurement of alkaline secretion.…”

Stimulatory Effect of Nitric Oxide on Bicarbonate Secretion in Bullfrog Duodenums in vitro

“…Since a gastric hyperemic response associated with acid back-diffusion is mediated by NO [27, 29], and since NO may activate COX activity leading to PG production, it might be possible that endogenous NO is involved in the regulatory mechanism of HCO – 3 response caused by mucosal acidification. Indeed, Holm et al [30]recently showed that the acid-induced HCO – 3 secretion in the rat duodenum was blocked by L -NAME, suggesting the involvement of an L -arginine/NO pathway in the mechanism.…”

The angiotensin II receptor type 2 agonist CGP 42112A stimulates NO production in the porcine jejunal mucosa

“…Johansson et al [4] demonstrated that rat duodenal mucosal bicarbonate secretion increased upon administration of the AT2-receptor agonist CGP42112A (0.1 μg kg -1 min -1 ). Furthermore, rat duodenal mucosal bicarbonate secretion has been shown to be regulated partly by NO [8]. …”