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Title of Journal: Pflugers Arch Eur J Physiol

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Abbravation: Pflügers Archiv - European Journal of Physiology

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Springer-Verlag

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DOI

10.1002/anie.201483471

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1432-2013

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Closure of multiple types of KSuperscript+/Supe

Authors: Charlotte Mehlin Sorensen Isaiah Giese Thomas Hartig Braunstein NielsHenrik HolsteinRathlou Max Salomonsson
Publish Date: 2011/08/27
Volume: 462, Issue: 5, Pages: 655-
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Abstract

Inhibition of K+ channels might mediate renal vasoconstriction As inhibition of a single type of K+ channel caused minor or no renal vasoconstriction in vivo in rats we hypothesized that several classes of K+ channels must be blocked to elicit renal vasoconstriction We measured renal blood flow RBF in vivo in anesthetized Sprague–Dawley rats Test agents were infused directly into the renal artery to avoid systemic effects Inhibition of BKCa and Kir channels with TEA and Ba2+ respectively caused small and transient reductions in RBF to 93 ± 2 and 95 ± 1 of baseline respectively KATP SKCa or Kv channel blockade with glibenclamide apamin and 4aminopyridine respectively was without effect However a cocktail of all blockers caused a massive reduction of RBF to 15 ± 10 of baseline Nifedipine and mibefradil abolished and reduced respectively this RBF reduction The effect of the cocktail of K+ channel blockers was confirmed in mice using the isolated bloodperfused juxtamedullary nephron preparation A cocktail of K+ channel openers K+ NS309 NS1619 and pinacidil had only a minor effect on baseline RBF in vivo in rats but reduced the vasoconstriction induced by bolus injections of norepinephrine or angiotensin II by 33 ± 5 and 60 ± 5 respectively Our results indicate that closure of numerous types of K+ channels could participate in the mediation of agonistinduced renal vasoconstriction Our results also suggest that renal vasoconstriction elicited by K+ channel blockade is mediated by nifedipinesensitive Ca2+ channels and partly by mibefradilsensitive Ca2+ channelsThe skilful technical assistance of Ms Cecilia Vallin is gratefully acknowledged This study was supported by the Danish National Research Foundation the Danish Heart Foundation the Lundbeck Foundation and the AP Møller Foundation for the Advancement of Medical Sciences


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