Abstract
Background Patients who undergo total colectomy with ileopouch anal reconstruction often have persistent diarrhea and frequent bowel movements. Analysis of the intestinal adaptation after total colectomy may lead to developing novel therapies for postoperative diarrhea. Methods Sprague-Dawley rats underwent total colectomy with ileoanal reconstruction and were sacrificed 4 and 8 weeks later. Mucosal response to aldosterone was evaluated with the use of ileal mucosa in an Ussing chamber by measuring short circuit current after in vitro stimulation with aldosterone. We investigated the expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD 2) in intestinal epithelial cells. To examine the role of hyperaldosteronism, we also evaluated rats treated with a sodium-deficient diet or subcutaneous aldosterone infusion. Results Aldosterone levels increased 80-fold after total colectomy. A comparable amount of aldosterone dramatically increased aldosterone-mediated, amiloride-sensitive short circuit current in the mucosa from colectomized rats, but not in control rats. We measured an increase in 11β-HSD 2 messenger RNA and protein in the distal ileum from colectomized rats. Circulating aldosterone appears to be essential for these functional and molecular changes because similar results were obtained by using the mucosa from both dietary sodium–depleted and aldosterone-infused rats. Conclusions Induction of 11β-HSD 2 is essential for enhanced mineralocorticoid action in the remnant ileum after total colectomy in rats.
Published Version
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