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Functional consequences at the single-nephron level of the lack of adenosine A1 receptors and tubuloglomerular feedback in mice

  • Renal Function, Body Fluids
  • Published:
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Abstract

Mice deficient for adenosine A1 receptors (A1AR) lack tubuloglomerular feedback (TGF). In vivo micropuncture experiments were performed under anesthesia in A1AR-deficient and wild-type littermate mice to study the effects of chronic absence of A1AR on fluid and Na+ reabsorption along the nephron, as well as the functional consequences at the single-nephron level of the lack TGF. Evidence is provided for an A1AR-mediated tonic inhibition of Na+ reabsorption in a water-impermeable segment of the loop of Henle, possibly the thick ascending limb. In contrast, proximal tubular reabsorption of fluid, Na+ and K+ was unaffected by the chronic absence of A1AR. Experiments in which artificial tubular fluid was added to free-flowing late-proximal tubules demonstrated an essential role of A1AR/TGF in the stabilization of fluid and Na+ delivery to the distal nephron. Further, the occurrence of spontaneous oscillations of hydrostatic pressure in proximal tubule (P PT) at a frequency of about 32 mHz depended on intact A1AR/TGF. In comparison, the normal, stabilizing reduction in P PT following the initial rise in P PT during sustained small increases in proximal tubular flow rate does not require A1AR/TGF; TGF-independent mechanisms appear to compensate in this regard for a lack of TGF under physiological conditions and the lack of TGF is unmasked only when supraphysiological flow rates overwhelm TGF-independent compensation.

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Acknowledgements

The authors gratefully acknowledge the support by Hartmut Osswald. This work was supported by grants provided by the Federal Ministry of Education and Research (BMBF 01KS9602) and the Interdisciplinary Center of Clinical Research Tübingen (IZKF).

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Author notes

  1. V. Vallon

    Present address: Division of Nephrology/Hypertension, University of California San Diego & VAMC, 3350 La Jolla Village Drive (9151), San Diego, CA 92161, USA

Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, University of Tübingen, Wilhelmstrasse 56, 72074, Tübingen, Germany

    V. Vallon, K. Richter, D. Y. Huang & T. Rieg

  2. NIDDK, NIH, Building 10, Room 4 D51, 10 Center Drive MSC 1370, Bethesda, MD, USA

    J. Schnermann

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  1. V. Vallon
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Correspondence to V. Vallon.

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Vallon, V., Richter, K., Huang, D.Y. et al. Functional consequences at the single-nephron level of the lack of adenosine A1 receptors and tubuloglomerular feedback in mice. Pflugers Arch - Eur J Physiol 448, 214–221 (2004). https://doi.org/10.1007/s00424-004-1239-8

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  • DOI: https://doi.org/10.1007/s00424-004-1239-8

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