Low salt intake increases adenosine type 1 receptor expression and function in the rat proximal tubule.
Adenosine mediates Na+ reabsorption in the proximal tubule (PT) and other segments by activating adenosine type 1 receptors (A1-AR). We tested the hypothesis that A1-AR in the PT 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 (LS; 0.03% Na, wt/wt)-, normal (NS; 0.3% Na)-, and high-salt (HS; 3.0% Na) diets for 1 wk. 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 (LA: 2.8 +/- 0.2 vs. NS: 2.1 +/- 0.2 nl.min(-1).mm(-1), 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(-1).mm(-1), 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. Expression of A1-AR mRNA and protein was higher (P < 0.01) in microdissected PTs in LS rats compared with 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.
Kulick
Aaron
A
Department of Medicine, Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20057, USA.
Panico
Carolina
C
Gill
Pritmohinder
P
Welch
William J
WJ
D000818:Animals; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D015854:Up-Regulation; D014882:Water-Electrolyte Balance / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
C097280:1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D017673:Sodium Chloride, Dietary; D014970:Xanthines