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 x 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 L-ARG. These results are consistent with the hypothesis that endogenous NO maintains a proabsorptive influence on water and ion transport in the ileum.