Duodenal mucosal alkaline secretion and the renin-angiotensin system. An experimental study in the rat.

Abstract

Gastric acid is an important factor in the digestive process but it is also a potential threat to the gastroduodenal mucosa. Several mechanisms act in concert to resist this aggressive challenge, one of them being the neutralising mucosal secretion of bicarbonate into an unstirred mucus layer covering the surface epithelium. An extended knowledge of the regulatory principles involved in the regulation of duodenal mucosal alkaline secretion is of great interest, as they may help to clarify the obscure pathophysiology behind common gastroduodenal disorders, like acid-related dyspepsia, with or without concomitant mucosal disease.The general aim of this thesis was to elucidate sympatho-adrenergic inhibition of duodenal mucosal alkaline secretion and to investigate possible interactions with the renin-angiotensin system. Effects on duodenal morphological integrity of luminal acid exposure during sympatho-inhibition of mucosal alkaline secretion were also investigated.Duodenal mucosal alkaline secretion was measured by an in vivo pH-stat technique on isolated duodenal segments in anaesthetised rats. Sympathetic outflow was increased by modest blood loss or electrical stimulation of the splanchnic nerves. The renin-angiotensin system was interfered with pharmacologically. Duodenal mucosal damage was assessed by both light and scanning electron microscopy.The investigation suggests that the sympatho-adrenergic inhibitory effect on duodenal mucosal alkaline secretion is not mediated directly at the epithelial cells, rather via activation of secretomotor neurons of the enteric nervous system. Furthermore, the renin-angiotensin system, probably by activation of peripheral angiotensin II type-1 receptors, prolongs the sympatho-adrenergic inhibition of duodenal mucosal alkaline secretion. On the other hand, activation of angiotensin II type-2 receptors located in the duodenal wall stimulates duodenal mucosal alkaline secretion. An inhibitor of the angiotensin converting enzyme increases duodenal mucosal alkaline secretion mainly via a bradykinin-dependent pathway, not related to the inhibition of the angiotensin II synthesis. Data also suggest that morphological changes of the duodenal mucosa, induced by moderate intraluminal acidity (10 mM HCl), is not influenced by hypovolemia. However, at higher acidities (100 mM HCl) the hypovolemia contributes to more severe mucosal damage.