The selective cyclooxygenase-2 inhibitor parecoxib markedly improves the ability of the duodenum to regulate luminal hypertonicity in anaesthetized rats

Aim: To examine whether the prevention of post-operative duodenal ileus by treatment with parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, affects the ability of the duodenum to respond to luminal hypertonicity. Methods: The proximal duodenums of anaesthetized rats were perfused with hypertonic NaCl solutions with osmolalities of 400, 500, 600 or 700 mOsm kg(-1), and the effects on mucosal permeability, motility, transepithelial net fluid flux and effluent osmolality were assessed in the absence (control) and presence of parecoxib. Results: Parecoxib-treated, but not control animals, exhibited duodenal contractions, which were reduced by the nicotinic receptor antagonists mecamylamine and hexamethonium and by perfusion with 700 mOsm kg(-1). All animals responded to luminal hypertonicity with induction of net fluid secretion, which peaked at an osmolality of 500 mOsm kg(-1). The hypertonicity-induced increases in fluid secretion were twofold greater in parecoxib-treated than in control rats and attenuated by nicotinic receptor blockade. The decrease in luminal osmolality correlated with the osmolality of the perfusion solution in both control and parecoxib-treated animals but the osmolality-adjusting capability was markedly better in the latter group. Rats exposed to duodenal luminal distension responded to hypertonicity with a greater fluid secretion and a larger decrease in luminal osmolality than control rats. Perfusion with 700 mOsm kg(-1) increased mucosal permeability in parecoxib-treated animals only, an effect abolished by nicotinic receptor blockade. Conclusion: Parecoxib markedly improved the ability of the duodenum to sense and to decrease luminal hypertonicity by a mechanism most probably involving inhibition of COX-2 and stimulation of nicotinic acetylcholine receptors.