Alimentary TractEnvironmental stress–induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat☆,☆☆,★
Section snippets
Animals
Male Wistar rats were purchased (Charles River, St. Constant, Quebec, Canada) and housed in the University of Calgary Animal Care Center. Animals were allowed to acclimatize to the facility for 2 weeks unless otherwise noted and were handled daily by the same individuals who performed the experiments. On most days the animals were housed in gang cages, but during permeability testing they were placed in individual metabolic cages for urine collection. To acclimatize them to this, the daily
Animal acclimatization
Transport of animals is a stressful situation, and we took advantage of this to sequentially follow gastrointestinal permeability after arrival at the Animal Care Center. These data are presented in a standard format illustrating the fractional excretion of sucrose (gastric permeability; Figure 1A), lactulose-mannitol ratio (small intestinal permeability; Figure 1B), and fractional excretion of sucralose (small intestinal and colonic permeability; Figure 1C).
Discussion
These data provide convincing support for the hypothesis that environmental stress can increase gastrointestinal permeability. Swimming stress constitutes a more profound form of stress than does restraint,24 and as illustrated in Figure 3, there was a significantly increased adrenal glucocorticoid response to this degree of stress. Not only was there a dose-response relationship between the degree of stress and plasma corticosterone concentration, but also with the elicited permeability
Acknowledgements
The authors thank Kim Tran, Tai Le, and Ian Gibbons for their technical expertise in the performance of these studies.
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Supported by generous grants from the Medical Research Council of Canada and Searle Canada Inc.
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Address requests for reprints to: Jon Meddings, M.D., 1705 Health Sciences Center, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1. e-mail: [email protected]; fax: (403) 220-8747.
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Dr. Meddings is an Alberta Heritage Foundation Medical Senior Scholar, and Dr. Swain is a Medical Research Council Medical Scholar and an AHFMR Clinical Investigator.