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Am J Physiol Renal Physiol (May 14, 2008). doi:10.1152/ajprenal.00061.2008
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Submitted on February 5, 2008
Accepted on April 29, 2008

Low Salt Intake Increases Adenosine type 1 Receptor Expression and Function in the Rat Proximal Tubule

Aaron Kulick1, Carolina Panico1, Pritmohinder S. Gill1, and William J. Welch1*

1 Nephrology & Hypertension, Georgetown University, Washington, District of Columbia, United States

* To whom correspondence should be addressed. E-mail: welchw{at}georgetown.edu.

Adenosine mediates Na+ reabsorption in the proximal tubule and other segments by activating adenosine type 1 receptors (A1-AR). We tested the hypothesis that A1-AR in the proximal tubule is regulated by salt intake and participates in the kidney adaptation to changes in salt intake. Absolute fluid reabsorption (Jv) was measured by direct in vivo microperfusion and recollection in rats maintained on low (0.03 %, Na w/w), normal (0.3% Na) and high (3.0% Na) diets for one week. The effect of microperfusion of BG9719, a highly selective inhibitor of A1-ARs or adenosine deaminase (AD), which metabolizes adenosine was measured in each group. Jv was higher in PT from LS rats (LS: 2.8±0.2 vs NS: 2.1±0.2 nl/min/mm, p<0.001). Jv in HS rats was not different from NS. BG9719 reduced Jv in LS rats by 66±6% (LS: 2.8±0.2 vs LS+CVT: 1.3±0.3 nl/min/mm, p<0.001), which was greater than its effect in NS (45±4%) or HS (41±4%) rats. AD reduced Jv similarly, suggesting that A1-ARs are activated by local production of adenosine. A1-AR mRNA and protein expression were higher (p<0.01) in microdissected PTs in LS rats compared to NS and HS. We conclude that A1-ARs in the PT are increased by low salt intake and that A1-AR participates in the increased PT reabsorption of solute and fluid in response to low salt intake.




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