Date of Award

4-1998

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Dr. Mary H. Perdue

Abstract

The gastrointestinal tract is particularly sensitive to stress. Stress-induced gastric ulceration and stress-induced alterations in motility have been examined. The purpose of my studies was to define stress-induced changes in the intestinal epithelium and the mechanisms involved in the epithelial responses. Wistar Kyoto rats were stressed by restraint. Jejunal and colonic tissues from stressed or control rats were removed and parametres of epithelial physiology were studied in Ussing chambers. Acute stress caused a significant increase in intestinal chloride ion secretion. In addition, tissues from stressed rats demonstrated impaired responses to neural activation. Compared to controls tissues from stressed rats were also found to have increased permeability to ions, and small inert probes, and increased permeability to a macromolecular protein. In spite of these functional abnormalities, the mucosa showed no signs of damange. Our next series of experiments showed that peripheral cholinergic nerves and corticotrophin releasing factor were responsible for mediating these epithelial responses to acute stress. Pretreatment with atropine (jejunum) or a corticotropin-releasing factor antagonist (colon) prevented the stress-induced pathophysiology, while administering corticotropin-releasing factor mimicked the colonic responses. These studies also showed that the Wistar Kyoto strain of rats developed more extreme intestinal abnormalities to stress than the parental Wistar strain, most likely due to the fact that Wistar Kyoto rats have less cholinesterase activity. In summary, my studies showed that stress impaired epithelial function along the intestinal tract. We speculate that in susceptible individuals, acute stress can cause the epithelial barrier to become leakly allowing greater uptake of small proinflammatory molecules (bacterial products) as well as larger macromolecules (antigens) from the lumen. Subsequent stimulation of immunocytes may initiate or exacerbate inflammation.

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