Abstracts
1999 Digestive Disease Week

# 2206 GENE INDUCTION OF 11b-HYDROXYSTEROID DEHYDROGENASE TYPE 2 (11b-HSD2) IS ESSENTIAL FOR ENHANCEMENT OF ALDOSTERONE-MEDIATED SODIUM ABSORPTION AFTER TOTAL PROCTOCOLECTOMY IN RATS
Shun Sato, Kohei Fukushima, K Koyama, I Sasaki, H Naito, Yuji Funayama, C Shibata, H Ogawa, Seiki Matsuno, Tohoku Univ Sch of Medicine, Sendai Japan

Background & Aims: Our previous data demonstrated the extremely increased levels of plasma aldosterone and induction of amiloride-sensitive sodium channel (ENaC) in remnant ileum after total proctocolectomy (GE:110:A339:1996). We hypothesized that altered sensitivity of epithelial cells to aldosterone would be the essential event to keep electrolyte balance in colectomized rats. The aim of this study was to investigate the contribution of aldosterone-mediated sodium absorption in remnant small intestine and kidney after total proctocolectomy. Methods: Male Sprague-Dawley rats underwent total proctocolectomy with ileo-anal anastomosis were necropsied at 4 and 8 weeks after the operation. The terminal ileal mucosae were mounted in Ussing chamber and amiloride (a blocker of ENaC)- and ouabain (an inhibitor of Na+-K+ ATPase)-sensitive short circuit current (Isc) were evaluated after the stimulation with aldosterone (10-7 M) for 8hrs. Alternatively, RNA was extracted from isolated epithelial cells of remnant small intestine and kidney. Gene expression of ENaC a-, b-, g-subunits, Na+-K+ ATPase a1-, b1-subunits and 11b-HSD2 was investigated by Northern blotting. Results: Mucosae from colectomized rats at 8 weeks showed the consistent enhancement of Isc by the addition of aldosterone into buffer, but control mucosae not. In addition, the mean amiloride-sensitive Isc measured after the stimulation was significantly (p=0.017) greater in colectomized rats than in control (40.3 vs. 10.4 mA/cm2). The mean ouabain-sensitive Isc was not significant between two groups. Remarkable induction of 11b-HSD2 gene was demonstrated at 4 weeks and persistent at 8 weeks in epithelial cells from remnant ileum. ENaC a- and g-subunit mRNAs were also induced after total proctocolectomy. However, the levels of Na+-K+ ATPase a1 - and b -subunit mRNAs were not affected by this procedure. On the other hand, the induction of all mRNAs including Na+-K+ ATPase a1- and b1-subunits were demonstrated in kidney samples from colectomized rats in a time-dependent fashion, Conclusion: Our data revealed that amiloride-sensitive sodium absorption mediated by aldosterone was enhanced in remnant ileal mucosae through the induction of ENaC mRNA. The induced gene expression of 11b-HSD2 which determine the specificity of aldosterone to its receptor may also participate in the accelerated sodium absorption. This is probably the case in kidney after total proctocolectomy since similar induction of 11b-HSD2 and ENaC mRNAs were observed. In conclusion, mineralocorticoid action enhanced by increased plasma aldosterone and the possible 11b-HSD2 effect is the primary event in the adaptive sodium absorption after total proctocolectomy.

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