Glomerular tubular balance is suppressed in adenosine type 1 receptor-deficient mice.
Glomerular tubular balance maintains a stable fractional solute and fluid reabsorption in the proximal tubule over a range of glomerular filtration rates. The mediators of this process are unknown. We tested the hypothesis that adenosine, produced in proximal tubule cells acting on adenosine type 1 receptors (A(1)-AR) promotes Na(+) and fluid uptake and mediates glomerular tubular balance. Absolute proximal fluid reabsorption (J(v)) was measured by in vivo microperfusion in A(1)-AR knockout and wild-type mice during perfusion of the closed proximal tubule at 2-10 nl/min. J(v) increased with perfusate flow from 2-4 nl/min in both strains, but the fractional increase was lower in A(1)-AR(-/-) mice (A(1)-AR(+/+): 114% vs. A(1)-AR(-/-): 38%; P < 0.001), suggesting reduced glomerular tubular balance (GTB). At higher perfusion rates, J(v) increased modestly in both strains, indicating less GTB at higher flow. The physiological effects of reduced GTB in A(1)-AR(-/-) mice were assessed from the response to an acute volume load (1 ml/2 min). Na(+) excretion and urine flow increased 76 and 73% more in A(1)-AR(-/-) mice than A(1)-AR(+/+) over the following 30 min, accompanied by a higher proximal tubule flow (A(1)-AR(-/-): 6.9 ± 0.9 vs. A(1)-AR(+/+): 5.2 ± 0.6 nl/min; P < 0.05). The expression of the sodium-hydrogen exchanger 3 and sodium phosphate cotransporter-2 were similar between strains. In conclusion, GTB is dependent on adenosine acting on type 1 receptors in the proximal tubule. This may contribute to acute changes in Na(+) and fluid reabsorption.
Bell
Tracy D
TD
Dept. of Medicine, Georgetown University, 4000 Reservoir Rd., Washington, DC 20057, USA.
Luo
Zaiming
Z
Welch
William J
WJ
D000241:Adenosine / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006439:Hemodynamics / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D066298:In Vitro Techniques; D007444:Inulin; D007678:Kidney Glomerulus / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009399:Nephrons / Q000502:physiology; D010477:Perfusion; D043682:Receptor, Adenosine A1 / Q000235:genetics* / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000378:metabolism; D014563:Urodynamics / Q000502:physiology
D043682:Receptor, Adenosine A1; C493558:Slc34a2 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D007444:Inulin; D012964:Sodium; D000241:Adenosine
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