Brasen, Jens Christian

Rasmussen, Kasper Møller

Salomonsson, Max

Sørensen, Charlotte Mehlin

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

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Downloaded from orbit.dtu.dk on: Dec 21, 2017Influence of K+-channels and gap junctions on endothelium derived hyperpolarization-induced renal vasodilation in ratsRasmussen, Kasper Møller; Brasen, Jens Christian; Salomonsson, Max; Sørensen, Charlotte MehlinPublished in:Acta PhysiologicaPublication date:2015Document VersionPublisher's PDF, also known as Version of recordLink back to DTU OrbitCitation (APA):Rasmussen, K. M., Brasen, J. C., Salomonsson, M., & Sørensen, C. M. (2015). Influence of K+-channels andgap junctions on endothelium derived hyperpolarization-induced renal vasodilation in rats. Acta Physiologica,215(Suppl. 703 - Meeting abstract), 13-13.strictor activity (functional sympatholysis) and areduced blood flow to contracting skeletal muscle. Toinvestigate to what extend a physically active lifestylecan offset these age related changes, we comparedinactive young with lifelong sedentary, moderatelyactive and very active elderly men at rest, duringcycling and one-legged knee-extensions and arterialinfusion of ACh, SNP and ATP with and withouttyramine (stimulates NA release). The vasodilatoryresponse to ACh was lowest in the sedentary elderly,higher in active elderly and highest in the young men,whereas ATP induced vasodilation was lower in thesedentary elderly only. During exercise, leg bloodflow, vascular conductance and VO2 was lower andleg lactate release higher in the sedentary elderly com-pared to the young, whereas there was no differencebetween the active elderly and young. Tyramine infu-sion lowered resting vascular conductance in allgroups, but only in the sedentary elderly during exer-cise. Tyramine did not alter the vasodilator responseto ATP infusion in any of the three groups. Infusionof the antioxidant N-acetylcysteine lowered arterialblood pressure, but did not alter blood flow duringexercise despite of an increased NO bioavailability.Plasma and skeletal muscle endothelin-1 was increasedin the sedentary elderly, but not in the active elderlycompared to young med. A lifelong physical activelifestyle can maintain a sufficient exercise hyperaemia,intact functional sympatholysis during exercise andvasodilator response to ATP despite a reduction inendothelial NO function.30Influence of K+-channels and gapjunctions on endothelium derivedhyperpolarization-induced renalvasodilation in ratsKasper Møller Rasmussen1, Jens Christian Brasen2,Max Salomonsson1, Charlotte Mehlin Sørensen11University of Copenhagen, Denmark; 2Technical Universityof Denmark, DenmarkWe investigated the role of Ca2+-activated K+-channelsin the endothelial derived hyperpolarization-inducedrenal vasodilation in vitro and in vivo in rats. Also,the possible role of K+- induced activation of inwardrectifier K+ (Kir) channels and Na+/K+-ATPase wasassessed. Furthermore, involvement of renal myoen-dothelial gap junctions was evaluated in vitro.Because assessment of endothelial derived hyperpo-larization-induced renal vasodilation in vivo is ham-pered by experimental limitations, we have combinedin vivo and in vitro experiments. Isometric tension inrat renal interlobar arteries was measured using a wiremyograph. Renal blood flow was measured in isoflu-rane and pentobarbital anesthetized rats. The ACh-in-duced response was measured before and afterinhibition of the nitric oxide synthase with L-NAMEand cyclooxygenase using indomethacin. Blockade ofsmall conductance Ca2+-activated K+-channels (SKCa)by apamin and intermediate conductance Ca2+-acti-vated K+-channels (IKCa) by TRAM-34 significantlydecreased the endothelial derived hyperpolarization-in-duced vasorelaxation in vitro but had no effectin vivo. Inhibition of Kir-channels by Ba2+ and Na+/K+-ATPases by ouabain significantly attenuated renalvasorelaxation in vitro but had no effect in vivo. Invitro, inhibition of gap junctions using carbenoxoloneor 18a-glycyrrhetinic acid significantly reduced theendothelial derived hyperpolarization-induced vasore-laxation. In conclusion we found that in vitro, renalvascular SKCa and IKCa-channels are essential for theendothelial derived hyperpolarization-induced vasore-laxation. Furthermore, activation of Kir-channels,Na+/K+-ATPases and vascular gap junctions play a sig-nificant role in the renal vascular endothelial derivedhyperpolarization-response in vitro. In vivo theendothelial derived hyperpolarization response seemsunaffected by the present blockade of various K+channels.31The role of the glomerularendothelium in kidney functionJenny Nystr€omUniversity of Gothenburg, SwedenThe glomerular endothelium (GEN) is a microvascularvessel bed lining the glomerular capillaries. The cellsare unusually flat, have a large cytoplasm and are den-sely attenuated by fenestrations. These fenestrationsdo not have a membrane as it has in many other cap-illary beds. The size of the fenestrae is in the range of60 nm. Since albumin molecules have a size of 3.6 nmno one has considered the GEN being a part of thepermselective barrier between blood and urine. Thishas changed since the role of the cell surface coat orglycocalyx has been investigated and described. It hasalso been suggested how this negatively charged layercontributes to permselectivity. Part from being animportant component of the permselective barrierbetween blood and urine the GEN participates in anelaborate cross talk with the other cellular compo-nents of the barrier. Factors produced by the closelysituated podocytes like VEGF affects the GEN andPDGF made by the GEN stimulate mesangial cells toproliferate. This cross talk is vital for the barrier func-tion and is disturbed in kidney disease. The glomeru-lar endothelium may be severely damaged in diseasesaffecting microvascular beds in the body or firstlyaffecting podocytes and depending on signaling inturn affects the GEN. Changes in vascular tone andstiffness, atherosclerosis and fibrosis are the down-stream effects of a disturbed cellular function leadingActa Physiol 2015, 215 (Suppl. 703), 1–21© 2015 The Authors. Acta Physiologica © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd 13Abstracts

Influence of K+-channels and gap junctions on endothelium derived hyperpolarization-induced renal vasodilation in rats

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Influence of K+-channels and gap junctions on endothelium derived hyperpolarization-induced renal vasodilation in rats

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