Manaf Sababi

Mucus and alkali secretion in the rat duodenum: Effects of indomethacin, Nω-Nitro-l-arginine, and luminal acid

BACKGROUND & AIMS Duodenal mucus and bicarbonate secretion appear to play an essential role in the protection of the duodenum. The aim of this study was to examine duodenal bicarbonate and mucus secretion and the effects of cyclooxygenase inhibition, nitric oxide synthase inhibition, and luminal acid. METHODS Duodenal mucus gel thickness was measured using microelectrodes during intravital microscopy in anesthetized rats. Bicarbonate secretion was measured using back-titration. RESULTS A continuous layer of mucus with a mean thickness of 284 +/- 11 microns (n = 35) and a mean alkaline secretion of 0.18 +/- 0.01 mumol.cm-2.min-1 were found in untreated animals. Indomethacin decreased both mucus and bicarbonate secretion by about 35%. NO synthase inhibition with N omega-nitro-L-arginine reduced mucus secretion by about 21% but increased bicarbonate secretion by 39%. Exposure of the mucosal surface to 10 mmol/L HCI increased mucus secretion by 44% and bicarbonate secretion by 22%. CONCLUSIONS The duodenal mucus layer is continuous. It can be easily removed, and new secretion can be followed. Duodenal mucus secretion is strongly stimulated by luminal acid and endogenous prostanoids and less markedly by NO, whereas bicarbonate secretion is stimulated by acid and endogenous prostanoids and inhibited by endogenous NO.

The duodenal motility response to HCl is influenced by NO and prostaglandins

Abstract In this study the following questions were addressed: (1) Does HCl affect duodenal motility in rats with postoperative ileus? (2) If so, at what luminal HCl concentration does this occur? (3) If HCl increases duodenal motility, is this effect associated with disturbance of mucosal integrity? (4) Do prostaglandins and NO affect the duodenal motility response to HCl? Proximal duodenum was perfused in situ with saline or HCl (3, 10 and 100 mM) in anesthetized rats. Duodenal motility was assessed by measuring intraluminal pressure and myoelectric activity. Mucosal integrity was determined as blood-to-lumen clearance of 51 Cr-EDTA. Rats were divided into four subgroups: (1) Controls; (2) rats treated with the nitric oxide synthase (NOS) inhibitor N ω -nitro-l-arginine-methyl-ester (L-NAME); (3) rats treated with the cyclooxygenase (COX) inhibitor indomethacin; and (4) rats treated with L-NAME and indomethacin. Very few duodenal contractions occurred during saline perfusion or in response to HCl in controls. The stimulatory effect of L-NAME on motility varied among animals. In L-NAME-treated rats motility was increased by 10 and 100 mM HCl, and in the latter case it subsequently decreased. Indomethacin induced motility in all animals. This effect was markedly reduced by perfusion with 10 and 100 mM HCl and transiently inhibited by the NO donor nitroprusside. In L-NAME+indomethacin-treated rats, 10 and 100 mM HCl decreased motility, but to a lesser extent than in rats treated with indomethacin alone. Only 100 mM HCl increased mucosal permeability in all groups. It is concluded that HCl does not affect duodenal motility in rats with postoperative ileus unless they are treated with inhibitors of NOS or of COX. HCl induces transmission of both excitatory and inhibitory signals to duodenal smooth muscle, and the inhibitory signals, mediated by prostaglandins and NO, predominate under control conditions. The threshold luminal [H + ] for its effect on duodenal motility appears to lie between 3 and 10 mM HCl. The HCl-induced changes in duodenal motility occur at a lower HCl concentration than that required to increase 51 Cr-EDTA permeability, suggesting that the motility response is not triggered by mucosal injury.