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Am J Physiol Renal Physiol (April 8, 2003). doi:10.1152/ajprenal.00073.2003
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Submitted on February 24, 2003
Accepted on March 20, 2003

Increased Collecting Duct Urea Transporter Expression in Dahl Salt Sensitive Rats

Robert A. Fenton1*, Chung-Lin Chou1, Shana Ageloff1, William Brandt1, John B. Stokes2, and Mark A. Knepper1

1 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institutes, National Institutes of Health, Bethesda, MD, USA
2 University of Iowa and Veterans Affairs Medical Center, Department of Internal Medicine, Iowa City, Iowa, USA

* To whom correspondence should be addressed. E-mail: Fentonr{at}nhlbi.nih.gov.

Since abnormalities of inner medullary function have been proposed in Dahl salt-sensitive (DS) rats versus salt-resistant (DR) rats, we performed transporter profiling by semi-quantitative immunoblotting to determine if specific solute transporter abundances are altered in inner medullas of DS rats versus DR rats. Although none of the expressed Na transporters were up-regulated in the inner medullas of DS rats compared to DR rats, there were marked increases in the protein abundances of the collecting duct urea transporters; UT-A1 (to 212% of DR) and UT-A3 (to 223% of DR). These differences were confirmed by immunocytochemistry. Quantitative real-time PCR showed higher mRNA abundance in DS rats for both UT-A1 (to 256% of DR) and UT-A3 (to 210% of DR). In isolated, perfused IMCDs, urea permeability was significantly greater in DS rats. Since both UT-A1 and UT-A3 are transcriptionally regulated by glucocorticoids, we measured both plasma corticosterone levels and inner medullary 11{beta}-hydroxysteroid dehydrogenase type 2 (11{beta}-HSD2) abundances. Although the plasma corticosterone concentrations were not different between DS and DR rats, immunoblotting and immunocytochemistry revealed a marked elevation of 11{beta}-HSD2 abundance in DS rats. Consistent with the view that an elevated 11{beta}-HSD2 level is responsible for increased urea transporter expression in the IMCD, administration of the 11{beta}-HSD2 inhibitor carbenoxolone to DS rats decreased the abundances of UT-A1 and UT-A3 to levels similar to those seen in DR rats.




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