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Published ahead of print on May 3, 2006
Journal of the American Society of Nephrology
© 2006 American Society of Nephrology
doi: 10.1681/ASN.2005121381
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Received December 30, 2005
Accepted on April 4, 2006

BASIC SCIENCE: Pathophysiology of Renal Disease and Progression

Hyperosmolality In Vivo Upregulates Aquaporin 2 Water Channel and Na-K-2Cl Co-Transporter in Brattleboro Rats

Chunling Li *, Weidong Wang *, Sandra N. Summer *, Melissa A. Cadnapaphornchai *{dagger}, Sandor Falk *, Fuminori Umenishi *, and Robert W. Schrier *1

Departments of *Medicine and {dagger}Pediatrics, University of Colorado School of Medicine, Denver, Colorado


1 To whom correspondence should be addressed. E-mail: robert.schrier{at}uchsc.edu.


   Abstract

There are considerable experimental results that indicate that arginine vasopressin (AVP)-independent factors are involved in urinary concentration. This study examined the role of hyperosmolality in vivo to modulate aquaporin 2 (AQP2) and Na-K-2Cl co-transporter (NKCC2), pivotal factors in urinary concentration, in AVP-deficient Brattleboro (BB) rats. Hyperglycemia with associated hyperosmolality occurred in diabetic BB rats (BBDM). Protein abundance of AQP2 increased and was reversed by insulin in the inner medulla (IM; control 100 ± 5%; BBDM 146 ± 8%; BBDM+Ins 122 ± 9%; P < 0.001) and inner stripe of outer medulla (ISOM; control 100 ± 4%; BBDM 123 ± 8%; BBDM+Ins 93 ± 6%; P < 0.05). These results were confirmed by immunohistochemistry studies. NKCC2 rose in the ISOM but was not reversed with insulin treatment. For investigation of the role of hyperosmolality in the absence of hyperglycemia on the regulation of the expression of renal AQP and NKCC2, studies were performed with hyperosmolality that was induced by 0.5% NaCl in drinking water in BB rats. Hyperosmolality that was induced by NaCl increased significantly the protein abundance of IM AQP2 (121 ± 2 versus 100 ± 5%; P < 0.01), ISOM AQP2 (135 ± 6 versus 100 ± 5%; P < 0.001), cortex plus outer stripe of outer medulla AQP2 (121 ± 4 versus 100 ± 1%; P < 0.001), ISOM NKCC2 (133 ± 1 versus 100 ± 4%; P < 0.05), and cortex plus outer stripe of outer medulla NKCC2 (142 ± 16 versus 100 ± 9%; P < 0.05). In conclusion, hyperosmolality, secondary to either glucose or NaCl, upregulated renal AQP2 and NKCC2 in vivo in BB rats.




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