Aim: Experiments were performed in anaesthetized rats to clarify the role of nitric oxide (NO) in the control of colonic permeability.
Methods: Colonic luminal pressure, the transmucosal potential difference (PD) and the clearance of [3H] mannitol and [14C] urea from blood to lumen were measured. NO synthesis was blocked with Nomega-nitro-L-arginine (L-NNA) i.v. and mucosal permeability was increased by deoxycholic acid (DCA, 4 mm). The involvement of histamine in the response was studied by giving the histamine H1 receptor blocker pyrilamine.
Results: In proximal colon, L-NNA per se increased luminal pressure and PD but had no significant effect on clearance. DCA per se increased luminal pressure, had no significant effect on PD, but increased mannitol and urea clearance and the clearance ratio. L-NNA and pyrilamine both blocked the luminal pressure effect of DCA but L-NNA had no significant effect on the clearance response to DCA. In distal colon, L-NNA per se had no significant effect on pressure and clearance, but increased PD like in proximal colon. DCA had no significant effect on luminal pressure, but markedly reduced PD and increased both clearance and clearance ratio. In this segment, L-NNA significantly potentiated the clearance response to DCA, and further increased clearance ratio to a value not significantly different from unity (1.00 +/- 0.05).
Conclusion: The data suggest that in vivo, moderate concentrations of bile acids increase colonic permeability in rats via a mechanism that is inhibited by NO in distal but not in proximal colon. In distal colon, NO may contribute to the maintenance of epithelial barrier function.