Endogenous Nitric Oxide Promotes Ileal Absorption

Abstract

Background/aims. Nitric oxide (NO) is generated in vascular endothelium and enteric neural plexuses from L-arginine by the action of nitric oxide synthase (NOS). This study tested the hypothesis that NO is a modulator of ileal water and ion transport. Methods. NADPH diaphorase staining was performed on fixed frozen sections of canine ileum. Absorption studies ( n = 80) were performed in five dogs with 25-cm ileal Thiry-Vella fistulas (TVF). Perfusion with [ 14C]PEG was used to calculate absorption of water, ions, and glucose from the TVF. Experiments comprised three 1-hr periods: basal, drug infusion, and recovery. Drugs infused luminally at 5 × 10 -4 mol/liter included l-ARG (NOS substrate), l -NAME (NOS inhibitor), l-ARG/ l-NAME combination, d -ARG (inactive enantiomer of l-ARG), l-LYS (basic amino acid control for l-ARG), and SNAP (NO donor). Results. NADPH diaphorase staining indicated NOS activity in the ileal mucosa and submucosa. l -ARG and SNAP caused significant increases in water and ion absorption, whereas l-NAME caused significant decreases. The prosecretory effect of l -NAME was completely reversed by synchronous l-ARG. d-ARG and l-LYS had no significant effects. No infused agent influenced [ 14C]PEG recovery. Conclusions. Inhibition 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 lARG. These results are consistent with the hypothesis that endogenous NO maintains a proabsorptive influence on water and ion transport in the ileum.