HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/F1135    most recent 00356.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Wang, W. Articles by Schrier, R. W. Search for Related Content PubMed PubMed Citation Articles by Wang, W. Articles by Schrier, R. W.

Molecular analysis of impaired urinary diluting capacity in glucocorticoid deficiency

Departments of ¹Medicine and ²Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado; and ³Division of Critical Care Nephrology, Chang Gung Memorial Hospital, Taipei, Taiwan

Submitted 30 August 2005 ; accepted in final form 5 December 2005

Urinary diluting ability and protein abundance of renal aquaporins (AQPs) and ion transporters in glucocorticoid-deficient (GD) rats were examined at baseline and in response to oral water loading. Rats underwent bilateral adrenalectomy followed by aldosterone (GD) or aldosterone + dexamethasone (CTL) replacement. Before oral water loading, urinary output was significantly decreased and urinary osmolality (U_osm) was increased in GD compared with CTL rats. Protein abundance of inner medullary AQP2 (148 ± 18%), phosphorylated AQP2 (pAQP2, 156 ± 13%), and AQP3 (145 ± 8%) was significantly upregulated in GD compared with CTL rats (all P < 0.05). GD rats also demonstrated a marked reduction in urinary Na⁺ excretion compared with pair-fed CTL rats. Na⁺-K⁺-2Cl^– cotransporter, Na⁺/H⁺ exchanger type 3, and cortical - and -subunits of the epithelial Na⁺ channel were significantly upregulated in GD rats. At 1 h after an acute water load (40 ml/kg by oral gavage), GD rats demonstrated a decrease in percent water excretion (5 ± 1 vs. 33 ± 9%, P < 0.01) and urinary output (33 ± 12 vs. 250 ± 65 µl·kg^–1·min^–1, P < 0.05) and an increase in U_osm (1,894 ± 292 vs. 316 ± 92 mosmol/kgH₂O, P < 0.001) compared with CTL rats. Plasma AVP was increased (1.6 ± 0.2 vs. 0.9 ± 0.2 pg/ml, P < 0.05), as was protein expression of inner medullary AQP2 (149 ± 5%) and pAQP2 (177 ± 9%, P < 0.01), in GD compared with CTL rats; apical expression of AQP2 was maintained in GD rats. The vasopressin V₂ receptor antagonist OPC-31260 increased percent water excretion and urinary output and reduced U_osm compared with vehicle-treated GD rats. OPC-31260 also reversed the increased abundance and apical trafficking of inner medullary AQP2 and pAQP2 protein in GD rats. In conclusion, enhanced protein abundance of Na⁺ transporters and Na⁺ channels with Na⁺ retention occurred with GD. OPC-31260 reversed upregulation and apical trafficking of AQP2 and pAQP2 in association with improved urinary diluting capacity and increased water excretion after oral water loading.

arginine vasopressin; aquaporin; impaired urinary dilution

This article has been cited by other articles:

				W. Wang, C. Li, S. N. Summer, S. Falk, W. Wang, D. Ljubanovic, and R. W. Schrier Role of AQP1 in endotoxemia-induced acute kidney injury Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1473 - F1480. [Abstract] [Full Text] [PDF]

				R. W. Schrier Body Water Homeostasis: Clinical Disorders of Urinary Dilution and Concentration J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1820 - 1832. [Full Text] [PDF]