ENDOGENOUS NITRIC-OXIDE PROMOTES ILEAL ABSORPTION

Background/aims. Nitric oxide (NO) is generated in vascular endotheliu m and enteric neural plexuses from L-arginine by the action of nitric oxide synthase (NOS). This study tested the hypothesis that NO is a mo dulator of ileal water and ion transport. Methods. NADPH diaphorase st aining was performed on fixed frozen sections of canine ileum. Absorpt ion studies (n = 80) were performed in five dogs with 25-cm ileal Thir y-Vella fistulas (TVF). Perfusion with [C-14]PEG was used to calculate absorption of water, ions, and glucose from the TVF. Experiments comp rised three 1-hr periods: basal, drug infusion, and recovery. Drugs in fused luminally at 5 X 10(-4) mol/liter included L-ARG (NOS substrate) , L-NAME (NOS inhibitor), L-ARG/L-NAME combination, D-ARG (inactive en antiomer of L-ARG), L-LYS (basic amino acid control for L-ARG), and SN AP (NO donor). Results. NADPH diaphorase staining indicated NOS activi ty in the ileal mucosa and submucosa. L-ARG and SNAP caused significan t increases in water and ion absorption, whereas L-NAME caused signifi cant decreases. The prosecretory effect of L-NAME was completely rever sed by synchronous L-ARG. D-ARG and L-LYS had no significant effects. No infused agent influenced [C-14]PEG recovery. Conclusions. Inhibitio n of endogenous NO synthesis by L-NAME causes a prosecretory response for water and ions, which can be reversed by the administration of NOS substrate L-ARG. These results are consistent with the hypothesis tha t endogenous NO maintains a proabsorptive influence on water and ion t ransport in the ileum. (C) 1995 Academic Press, Inc.