We investigated the role of Ca2+-activated K+ -channels in the endothelial derived hyperpolarization-induced renal vasodilation in vitro and in vivo in rats. Also, the possible role of K+ - induced activation of inward rectifier K+ (Kir) channels and Na+ /K+ -ATPase was assessed. Furthermore, involvement of renal myoendothelial gap junctions was evaluated in vitro. Because assessment of endothelial derived hyperpolarization-induced renal vasodilation in vivo is hampered by experimental limitations, we have combined in vivo and in vitro experiments. Isometric tension in rat renal interlobar arteries was measured using a wire myograph. Renal blood flow was measured in isoflurane and pentobarbital anesthetized rats. The ACh-induced response was measured before and after inhibition of the nitric oxide synthase with L-NAME and cyclooxygenase using indomethacin. Blockade of small conductance Ca2+-activated K+ -channels (SKCa) by apamin and intermediate conductance Ca2+-activated K+ -channels (IKCa) by TRAM-34 significantly decreased the endothelial derived hyperpolarization-induced vasorelaxation in vitro but had no effect in vivo. Inhibition of Kir-channels by Ba2+ and Na+ / K+ -ATPases by ouabain significantly attenuated renal vasorelaxation in vitro but had no effect in vivo. In vitro, inhibition of gap junctions using carbenoxolone or 18a-glycyrrhetinic acid significantly reduced the endothelial derived hyperpolarization-induced vasorelaxation. In conclusion we found that in vitro, renal vascular SKCa and IKCa-channels are essential for the endothelial derived hyperpolarization-induced vasorelaxation. Furthermore, activation of Kir-channels, Na+ /K+ -ATPases and vascular gap junctions play a significant role in the renal vascular endothelial derived hyperpolarization-response in vitro. In vivo the endothelial derived hyperpolarization response seems unaffected by the present blockade of various K+ channels.
|Issue number||Suppl. 703 - Meeting abstract|
|Publication status||Published - 2015|
|Event||Meeting on Endothelium-Dependent Hyperpolarizations in Health and Disease - Nyborg, Denmark|
Duration: 14 Sep 2015 → 17 Sep 2015
|Workshop||Meeting on Endothelium-Dependent Hyperpolarizations in Health and Disease|
|Period||14/09/2015 → 17/09/2015|