NITRIC-OXIDE MODULATES WATER AND ELECTROLYTE TRANSPORT IN THE ILEUM

Objective To test the hypothesis that nitric oxide is a modulator of i leal water and ion transport. Summary Background Data Nitric oxide is produced in the vascular endothelium and enteric neural plexuses of th e intestine and is involved in gastrointestinal motility and smooth mu scle contractility. Little is known about the role of nitric oxide in intestinal epithelial transport. Methods Ten-centimeter rabbit ileal s egments (n = 50) were vascularly perfused with an electrolyte solution containing red cells. The lumen was perfused with a solution containi ng C-14-PEG. Net fluxes of water and ions were calculated during three 20-minute periods: basal, drug infusion, and recovery. Perfusion pres sure was recorded to document changes in vascular resistance. Agents i nfused included the nitric oxide synthase substrate L-arginine, the ni tric oxide source sodium nitroprusside, the substrate control D-argini ne, and the nitric oxide synthase inhibitor N-G-nitro-L-arginine methy l 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-ar ginine. Infusion of D-arginine had no effect. Both L-arginine and sodi um nitroprusside caused mild vasodilation. Conclusions Inhibition of e ndogenous nitric oxide synthesis by N-G-nitro-L-arginine methyl ester causes secretion of water and ions. This secretion is reversed by admi nistration of the nitric oxide synthase substrate L-arginine. These fi ndings are consistent with the hypothesis that endogenous nitric oxide has a proabsorptive influence over the ileum in the basal state.