In vitro changes in the properties of rabbit colonic muscularis mucosae in colitis

Abstract

Background: The muscularis mucosae is the muscle layer closet to the site of elevated inflammatory mediator production in inflammatory bowel disease. Thus, it is the first muscle layer subject to their influence.

Methods: Using a rabbit trinitrobenzene sulfonic acid model of colitis, changes in the properties of the muscularis mucosae resulting from the inflammatory process were studied in vitro.

Results: Animals developed a mild colitis-like inflammation that was confined to the epithelium, lamina propria, and submucosa. Colitic muscularis mucosae contractile responses to leukotriene D4 and prostaglandins E2 and F2 alpha were significantly attenuated relative to the maximum tissue response to acetylcholine, whereas responses to histamine, substance P, and vasoactive intestinal polypeptide were unchanged. In addition, the stress-generating capacity of the colitic muscularis mucosae was compromised in a stimulus-independent manner and passive tension increased relative to active tension.

Conclusions: The muscularis mucosae undergoes two significant alterations in colitis: (a) a selective desensitization to the effects of arachidonic acid metabolites and (b) an impairment of its excitation-contraction coupling mechanism. A loss of the ability of the muscularis mucosae to cause mucosal movement and alter luminal surface area may be an important early stage in the pathophysiology of inflammatory bowel disease.