Abstract: | The effects of enalaprilate on duodenal mucosalalkaline secretion (in situ titration) and mean arterialblood pressure were investigated inchloralose-anesthetized male rats. A bolus injection ofenalaprilate (0.7 mg/kg intravenously) increased alkalinesecretion by about 60%, and this response was resistantto guanethidine (5 mg/kg intravenously),splanchnicotomy, and vagotomy. Furthermore, angiotensinII infusion (0.25-2.5 g/kg/hr intravenously)following the administration of enalaprilate failed toinfluence this response. Bradykinin (10-6-10-4 M) applied topically to theserosal surface of the duodenal segment under study increased dose-dependentlythe duodenal mucosal alkaline secretion, an effect thatcould be blocked by the selective bradykinin receptorsubtype-2 antagonist HOE140 (100 nmol/kg intravenously). HOE140 also antagonized the response toenalaprilate. These data suggest that enalaprilateincreases duodenal mucosal alkaline secretion via alocal bradykinin pathway involving receptors of thebradykinin receptor subtype-2 antagonist, rather than byblockade of endogenous angiotensin II or by centralautonomic neural regulation. |