Contribution of K+ channels to endothelium-derived hypolarization-induced renal vasodilation in rats in vivo and in vitro

  • Kasper Moller Boje Rasmussen
  • Thomas Hartig Braunstein
  • Max Salomonsson
  • Jens Christian Brasen
  • Charlotte Mehlin Sorensen
Integrative physiology


We investigated the mechanisms behind the endothelial-derived hyperpolarization (EDH)-induced renal vasodilation in vivo and in vitro in rats. We assessed the role of Ca2+-activated K+ channels and whether K+ released from the endothelial cells activates inward rectifier K+ (Kir) channels and/or the Na+/K+-ATPase. Also, involvement of renal myoendothelial gap junctions was evaluated in vitro. Isometric tension in rat renal interlobar arteries was measured using a wire myograph. Renal blood flow was measured in isoflurane anesthetized rats. The EDH response was defined as the ACh-induced vasodilation assessed after inhibition of nitric oxide synthase and cyclooxygenase using L-NAME and indomethacin, respectively. After inhibition of small conductance Ca2+-activated K+ channels (SKCa) and intermediate conductance Ca2+-activated K+ channels (IKCa) (by apamin and TRAM-34, respectively), the EDH response in vitro was strongly attenuated whereas the EDH response in vivo was not significantly reduced. Inhibition of Kir channels and Na+/K+-ATPases (by ouabain and Ba2+, respectively) significantly attenuated renal vasorelaxation in vitro but did not affect the response in vivo. Inhibition of gap junctions in vitro using carbenoxolone or 18α-glycyrrhetinic acid significantly reduced the endothelial-derived hyperpolarization-induced vasorelaxation. We conclude that SKCa and IKCa channels are important for EDH-induced renal vasorelaxation in vitro. Activation of Kir channels and Na+/K+-ATPases plays a significant role in the renal vascular EDH response in vitro but not in vivo. The renal EDH response in vivo is complex and may consist of several overlapping mechanisms some of which remain obscure.


Calcium activated K+ channels Endothelial-derived hyperpolarization Renal Vasodilation 



The skillful technical assistance of Ms. Cecilia Vallin, Ms. Nadia Soori, and Mr. Kristoffer Racz is gratefully acknowledged. We acknowledge the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen. This study was supported by the Danish National Research Foundation, the Danish Heart Foundation, and the A.P Møller Foundation for the Advancement of Medical Sciences.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Institute of Biomedical Sciences, Division of Renal and Vascular PhysiologyUniversity of CopenhagenCopenhagenDenmark
  2. 2.Department of Electrical EngineeringTechnical University of DenmarkKgs. LyngbyDenmark

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