Acid-induced increase in duodenal mucosal permeability is augmented by nitric oxide inhibition and vasopressin.

The aim of the study was to determine if and by what mechanism(s) nitric oxide inhibition modulates the susceptibility of the duodenum to hydrochloric acid-induced disturbances of mucosal integrity. A second aim was to investigate whether basal permeability is a determinant of epithelial acid barrier function. Using an in situ duodenal perfusion model, mucosal permeability, alkaline secretion and morphology were investigated in anaesthetized rats. Luminal perfusion with 50 mM hydrochloric acid increased duodenal mucosal permeability in the control animals. In animals receiving the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME 3 mg kg(-1) and 1 mg kg(-1) h(-1)) and in those receiving vasopressin (1 IU kg(-1) h(-1)), however, the mean increase in permeability in response to acid was markedly higher. In rats treated with either hexamethonium (20 mg kg(-1)) or atropine (0.5 mg kg(-1)) L-NAME failed to augment the acid-induced increase in permeability. Perfusion with hypotonic saline (25 mM) increased basal permeability but did not influence the response to acid. Exposure of the duodenum to hydrochloric acid caused very subtle changes of duodenal morphology. It is concluded that both inhibition of endogenous nitric oxide synthesis and vasopressin treatment augment the acid-induced increase in mucosal permeability. The mechanisms involved may be related to changes of Starling forces in the microcirculatory bed. Endogenous nitric oxide may protect the duodenal mucosa by regulating vascular permeability and interstitial fluid pressure.