title: Contribution of K(+) channels to endothelium-derived hypolarization-induced renal vasodilation in rats in vivo and in vitro.
abstract: 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 Ca(2+)-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 Ca(2+)-activated K(+) channels (SKCa) and intermediate conductance Ca(2+)-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 Ba(2+), 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.
authors.affiliation: Institute of Biomedical Sciences, Division of Renal and Vascular Physiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kasper Moller Boje
authors.initials: KMB
authors.lastname: Rasmussen
authors.affiliation: Institute of Biomedical Sciences, Division of Renal and Vascular Physiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas Hartig
authors.initials: TH
authors.lastname: Braunstein
authors.affiliation: Institute of Biomedical Sciences, Division of Renal and Vascular Physiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Max
authors.initials: M
authors.lastname: Salomonsson
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark, Ørsteds Plads 349, 2800, Kgs. Lyngby, Denmark. jcbra@elektro.dtu.dk.
authors.forename: Jens Christian
authors.identifier: http://orcid.org/0000-0003-4446-6331
authors.initials: JC
authors.lastname: Brasen
authors.affiliation: Institute of Biomedical Sciences, Division of Renal and Vascular Physiology, University of Copenhagen, Copenhagen, Denmark. cmehlin@sund.ku.dk.
authors.forename: Charlotte Mehlin
authors.initials: CM
authors.lastname: Sorensen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D024681:Potassium Channels, Calcium-Activated; D011720:Pyrazoles; C411671:TRAM 34; C119129:18alpha-glycyrrhetinic acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D002229:Carbenoxolone; D000109:Acetylcholine; D006034:Glycyrrhetinic Acid; D019331:NG-Nitroarginine Methyl Ester
keywords: Calcium activated K+ channels; Endothelial-derived hyperpolarization; Renal; Vasodilation