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In vivo stimulation of AMP-activated protein kinase enhanced tubuloglomerular feedback but reduced tubular sodium transport during high dietary NaCl intake

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Abstract

AMP-activated protein kinase (AMPK) is expressed in the apical membrane of cortical thick ascending limb, distal, and collecting tubules as well as macula densa cells of the kidneys. AMPK is an active modulator of epithelial Na+ channels, Na+–2Cl−–K+ cotransporter, and the ATP-dependent potassium channel. The present experiments explored whether AMPK participates in the regulation of tubuloglomerular feedback (TGF) and renal tubular sodium handling. To this end, renal clearance and micropuncture experiments were performed in anesthetized rats. Under normal NaCl diet, neither TGF response nor renal fluid and sodium excretion were altered by pharmacological activation of AMPK in vivo. However, under high NaCl diet, the TGF response was significantly enhanced after intravenous or intratubular application of the AMPK activator AICAR. Moreover, AICAR application significantly increased fractional delivery of fluid and sodium to the end of the proximal tubule. High dietary NaCl intake increased the renal transcript levels encoding the AMPK-α1 subunit, while it decreased the expression of AMPK-β1 and AMPK-γ2 subunits. Immunoblots revealed that high dietary NaCl intake reduced renal expression of activated AMPK by about three times compared to normal NaCl diet whereas additional AICAR application increased AMPK activity. Our results suggest that AMPK regulates tubuloglomerular balance as well as tubular transport upon change of renal work load.

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Acknowledgments

This work was supported by the DFG (HU1600/1-1 and HU1600/1-2).

Conflict-of-interest disclosure statement

All authors have read and approved the submission of the manuscript; the manuscript has not been published and is not being considered for publication elsewhere, in whole or in part, in any language, except as an abstract.

All authors state that there are no potential conflicts of interest in all relationships to the manuscript that could be perceived as real or apparent conflict(s).

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Authors and Affiliations

  1. Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard-Karls-University Hospitals and Clinics, and Interfaculty Centre of Pharmacogenomics and Pharmaceutical Research, University of Tübingen, Wilhelmstr. 56, 72074, Tübingen, Germany

    Dan Yang Huang, Huanhuan Gao, Hartmut Osswald & Bernd Nürnberg

  2. Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Krishna M. Boini & Florian Lang

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  1. Dan Yang Huang
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  2. Huanhuan Gao
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  3. Krishna M. Boini
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Correspondence to Dan Yang Huang.

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Dan Yang Huang and Huanhuan Gao shared first authorship.

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Huang, D.Y., Gao, H., Boini, K.M. et al. In vivo stimulation of AMP-activated protein kinase enhanced tubuloglomerular feedback but reduced tubular sodium transport during high dietary NaCl intake. Pflugers Arch - Eur J Physiol 460, 187–196 (2010). https://doi.org/10.1007/s00424-010-0803-7

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  • DOI: https://doi.org/10.1007/s00424-010-0803-7

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