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.
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Article info
Publication history
Accepted:
March 11,
2004
Sendai, Japan, and Prahran, Victoria, AustraliaFootnotes
☆Supported by Grant-in-Aid for Scientific Research 10557118 (K. Fukushima) and 07457266 (I. Sasaki) from the Ministry of Education, Science and Culture of Japan, Crohn and Colitis Foundation of America (K. Fukushima), and Kanae Foundation (K. Fukushima).
Identification
Copyright
© 2005 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
