NITRIC-OXIDE MODULATES WATER AND ELECTROLYTE TRANSPORT IN THE ILEUM

Objective To test the hypothesis that nitric oxide is a modulator of ileal water and ion transport. Summary Background Data Nitric oxide is produced in the vascular endothelium and enteric neural plexuses of the intestine and is involved in gastrointestinal motility and smooth muscle contractility. Little is known about the role of nitric oxide in intestinal epithelial transport. Methods Ten-centimeter rabbit ileal segments (n = 50) were vascularly perfused with an electrolyte solution containing red cells. The lumen was perfused with a solution containing C-14-PEG. Net fluxes of water and ions were calculated during three 20-minute periods: basal, drug infusion, and recovery. Perfusion pressure was recorded to document changes in vascular resistance. Agents infused included the nitric oxide synthase substrate L-arginine, the nitric oxide source sodium nitroprusside, the substrate control D-arginine, and the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester. Results L-arginine and sodium nitroprusside caused absorption of water and ions. NG-nitro-L-arginine methyl ester caused secretion of water and ions, which was prevented by synchronous infusion of L-arginine. Infusion of D-arginine had no effect. Both L-arginine and sodium nitroprusside caused mild vasodilation. Conclusions Inhibition of endogenous nitric oxide synthesis by N-G-nitro-L-arginine methyl ester causes secretion of water and ions. This secretion is reversed by administration of the nitric oxide synthase substrate L-arginine. These findings are consistent with the hypothesis that endogenous nitric oxide has a proabsorptive influence over the ileum in the basal state.