Electrolyte handling in the isolated perfused rat kidney: demonstration of vasopressin V2-receptor-dependent calcium reabsorption

  • Krister Bamberg Translational Sciences and Experimental Medicines, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden http://orcid.org/0000-0002-0538-6083
  • Lena William-Olsson Bioscience Renal, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden http://orcid.org/0000-0002-2604-2183
  • Ulrika Johansson Bioscience Renal, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
  • Anders Arner Department of Clinical Sciences Lund, Lund University, Lund, Sweden http://orcid.org/0000-0003-1386-090X
  • Judith Hartleib-Geschwindner Projects, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
  • Johan Sällström Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Keywords: AVP, ENaC, kidney, vasopressin

Abstract

Background: The most profound effect of vasopressin on the kidney is to increase water reabsorption through V2-receptor (V2R) stimulation, but there are also data suggesting effects on calcium transport. To address this issue, we have established an isolated perfused kidney model with accurate pressure control, to directly study the effects of V2R stimulation on kidney function, isolated from systemic effects.

Methods: The role of V2R in renal calcium handling was studied in isolated rat kidneys using a new pressure control system that uses a calibration curve to compensate for the internal pressure drop up to the tip of the perfusion cannula.

Results: Kidneys subjected to V2R stimulation using desmopressin (DDAVP) displayed stable osmolality and calcium reabsorption throughout the experiment, whereas kidneys not administered DDAVP exhibited a simultaneous fall in urine osmolality and calcium reabsorption. Epithelial sodium channel (ENaC) inhibition using amiloride resulted in a marked increase in potassium reabsorption along with decreased sodium reabsorption.

Conclusions: A stable isolated perfused kidney model with computer-controlled pressure regulation was developed, which retained key physiological functions. The preparation responds to pharmacological inhibition of ENaC channels and activation of V2R. Using the model, the dynamic effects of V2R stimulation on calcium handling and urine osmolality could be visualised. The study thereby provides evidence for a stimulatory role of V2R in renal calcium reabsorption.

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Published
2020-08-19
How to Cite
Bamberg, K., William-Olsson, L., Johansson, U., Arner, A., Hartleib-Geschwindner, J., & Sällström, J. (2020). Electrolyte handling in the isolated perfused rat kidney: demonstration of vasopressin V2-receptor-dependent calcium reabsorption. Upsala Journal of Medical Sciences, 125(4), 274–280. https://doi.org/10.1080/03009734.2020.1804496
Section
Original Articles