Inhibitory effect of experimental colitis on fluid absorption in rat jejunum:: role of the enteric nervous system, VIP, and nitric oxide

Impairment of small intestinal absorption has been described in patients with ulcerative colitis and in animal models of experimental colitis. The pathophysiology of this dysfunction has not been elucidated. The aim of this study was to investigate the effect of chemical colitis on jejunal fluid absorption and determine the role of the enteric nervous system and some putative neurotransmitters. In a rat model of iodoacetamide-induced colitis, jejunal net fluid absorption was evaluated by the in vivo single-pass perfusion technique. The effects of 1) tetrodotoxin (TTX), 2) benzylalkonium chloride (BAC), 3) capsaicin, 4) vasoactive intestinal polypeptide ( VIP) antagonism, 5) nitric oxide ( NO) synthase ( NOS) inhibition, and 6) 5-hydroxytryptamine type 3 and 4 (5-HT3 and 5-HT4) receptor antagonism on the changes in fluid movement were investigated. A significant decrease in jejunal net fluid absorption was found 2 and 4 days after colitis induction: 26 (SD 14) and 28 (SD 19) mu l center dot min(-1) center dot g dry intestinal wt(-1), respectively [P < 0.0002 compared with sham rats at 61 (SD 6.5) mu l center dot min(-1) center dot g dry intestinal wt(-1)]. No histological changes were evident in jejunal sections. TTX and BAC reversed this decrease in fluid absorption: 54 ( SD 13) and 44 (SD 14) mu l center dot min(-1) center dot g dry intestinal wt(-1) (P = 0.0005 and P = 0.019, respectively, compared with colitis). Ablation of capsaicin-sensitive primary afferent fibers had a partial effect: 45 (SD 5) mu l center dot min(-1) center dot g dry intestinal wt(-1) (P = 0.001 and P = 0.003 compared with colitis and sham, respectively). Constitutive and neuronal NOS inhibition and VIP antagonism returned jejunal net fluid absorption to normal values: 66 (SD 19), 61 (SD 5), and 56 (SD 14) mu l center dot min(-1) center dot g dry intestinal wt(-1), respectively. 5-HT3 and 5-HT4 receptor antagonism had no effect. Chemical colitis is associated with a significant decrease in jejunal net fluid absorption. This decrease is neurally mediated and involves VIP- and NO-related mechanisms.