Submitted on June 10, 2005
Accepted on August 18, 2005
Inhibitory Effect of Experimental Colitis on Fluid Absorption in Rat Jejunum: Role of The Enteric Nervous System, VIP And Nitric Oxide
Fadi H. Mourad1*, Kassem A. Barada1, Nadine A. Bou Rached2, Carmen I. Khoury2, Nayef E. Saade2, and Camille F. Nassar2
1 Department of Internal Medicine, American University of Beirut Faculty of Medicine, Beirut, Lebanon; Department of Physiology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
2 Department of Physiology, American University of Beirut Faculty of Medicine, Beirut, Lebanon
* To whom correspondence should be addressed. E-mail: fmourad{at}aub.edu.lb.
Background and Aims: 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. Methods: A rat model of
iodoacetamide-induced colitis was used. Jejunal net fluid absorption was evaluated by the
in-vivo single pass perfusion technique. The effects of i) tetrodotoxin (TTX), ii)
benzylalkonium chloride (BAC), iii) capsaicin, iv) VIP antagonism (VIPa), v) nitric oxide
synthase (NOS) inhibition and vi) 5-HT3 and 5-HT4 receptor antagonism on the changes in
fluid movement were investigated. Results: A significant decrease in jejunal net fluid
absorption was found at 2 and 4 days after colitis induction [mean 26(SD 14) and 28(19),
respectively; p<0.0002 as compared to sham rats 61(6.5) µl min-1 g-1 dry intestinal weight]. No
evident histologic changes were seen in jejunal sections. TTX and BAC reversed this decrease
in fluid absorption [54(13) and 44(14); p=0.0005 and p=0.019, respectively as compared to
colitis]. Ablation of capsaicin sensitive primary afferent fibers had a partial effect [45(5);
p=0.001 and p=0.003 compared to colitis and sham, respectively). Constitutive and neuronal
NOS inhibition and VIPa returned jejunal net fluid absorption to normal values [66(19), 61(5)
and 56(14), respectively]. 5-HT3 and 5H-T4 receptor antagonism had no effect. Conclusion:
Chemical colitis is associated with a significant decrease in jejunal net fluid absorption. This
decrease is neurally mediated and involves both VIP and NO related mechanisms.
