Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo

Ildikó Gödény; Piero Pollesello; István Édes; Zoltán Papp; Zsolt Bagi

doi:10.1016/S1734-1140(13)71488-9

Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo

Ildikó Gödény, Piero Pollesello, István Édes, Zoltán Papp, Zsolt Bagi

Physiology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Background: Levosimendan and its long-lived metabolite OR-1896 produce vasodilation in different types of vessels by activating ATP-sensitive (KATP) and other potassium channels. Methods: In the present study we applied intravital videomicroscopy to investigate the in situ effects of levosimendan and OR-1896 on the diameters of real resistance arterioles (rat cremaster muscle arterioles with diameters of ~ 20 μm). Results: Levosimendan and OR-1896 induced concentration-dependent (1 nM - 100 μM) dilations to similar extents in these arterioles (maximal dilation from 23 ± 2 to 33 ± 2 μm and from 22 ± 1 to 32 ± 1 μm, respectively). The arteriolar dilations induced by the selective KATP channel opener pinacidil (1 nM - 10 μM) (maximal dilation from 22 ± 4 μm to 35 ± 3 μm) were diminished in the presence of the selective KATP channel blocker - glibenclamide (5 μM) (maximal diameter attained: 22 ± 1 μm). Glibenclamide also counteracted the maximal dilations in response to levosimendan or OR-1896 (to 23 ± 3 μm or 22 ± 5 μm, respectively). Conclusions: In conclusion, this is the first demonstration that levosimendan and OR-1896 elicit arteriolar dilation in vivo, via activation of KATP channels in real resistance vessels in the rat.

Original language	English (US)
Pages (from-to)	1304-1310
Number of pages	7
Journal	Pharmacological Reports
Volume	65
Issue number	5
DOIs	https://doi.org/10.1016/S1734-1140(13)71488-9
State	Published - 2013

Keywords

Cremaster muscle
Intravital microscopy
KATP channels
Levosimendan
OR-1896
Vasodilation

ASJC Scopus subject areas

Pharmacology

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10.1016/S1734-1140(13)71488-9

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@article{71a1686981e244c0b6e96fdd7c52afb5,

title = "Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo",

abstract = "Background: Levosimendan and its long-lived metabolite OR-1896 produce vasodilation in different types of vessels by activating ATP-sensitive (KATP) and other potassium channels. Methods: In the present study we applied intravital videomicroscopy to investigate the in situ effects of levosimendan and OR-1896 on the diameters of real resistance arterioles (rat cremaster muscle arterioles with diameters of ~ 20 μm). Results: Levosimendan and OR-1896 induced concentration-dependent (1 nM - 100 μM) dilations to similar extents in these arterioles (maximal dilation from 23 ± 2 to 33 ± 2 μm and from 22 ± 1 to 32 ± 1 μm, respectively). The arteriolar dilations induced by the selective KATP channel opener pinacidil (1 nM - 10 μM) (maximal dilation from 22 ± 4 μm to 35 ± 3 μm) were diminished in the presence of the selective KATP channel blocker - glibenclamide (5 μM) (maximal diameter attained: 22 ± 1 μm). Glibenclamide also counteracted the maximal dilations in response to levosimendan or OR-1896 (to 23 ± 3 μm or 22 ± 5 μm, respectively). Conclusions: In conclusion, this is the first demonstration that levosimendan and OR-1896 elicit arteriolar dilation in vivo, via activation of KATP channels in real resistance vessels in the rat.",

keywords = "Cremaster muscle, Intravital microscopy, KATP channels, Levosimendan, OR-1896, Vasodilation",

author = "Ildik{\'o} G{\"o}d{\'e}ny and Piero Pollesello and Istv{\'a}n {\'E}des and Zolt{\'a}n Papp and Zsolt Bagi",

note = "Funding Information: ZB acknowledges support from the British Heart Foundation, Centre of Research Excellence, Oxford (RE/08/004) . The work was supported by the projects T{\'A}MOP 4.2.1./B-09/1/KONV-2010-0007, T{\'A}MOP 4.2.2./B-10/1-2010-024 and T{\'A}MOP-4.2.2.A-11/1/ KONV-2012-0045 (to ZP), implemented through the New Hungary Development Plan, co-financed by the European Social Fund and by a grant from National Heart, Lung, and Blood Institute R01HL104126 (to ZB). The authors would like to thank David Durham for the English language edition.",

year = "2013",

doi = "10.1016/S1734-1140(13)71488-9",

language = "English (US)",

volume = "65",

pages = "1304--1310",

journal = "Pharmacological Reports",

issn = "2299-5684",

publisher = "Polish Academy of Sciences Publishing House",

number = "5",

}

TY - JOUR

T1 - Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo

AU - Gödény, Ildikó

AU - Pollesello, Piero

AU - Édes, István

AU - Papp, Zoltán

AU - Bagi, Zsolt

N1 - Funding Information: ZB acknowledges support from the British Heart Foundation, Centre of Research Excellence, Oxford (RE/08/004) . The work was supported by the projects TÁMOP 4.2.1./B-09/1/KONV-2010-0007, TÁMOP 4.2.2./B-10/1-2010-024 and TÁMOP-4.2.2.A-11/1/ KONV-2012-0045 (to ZP), implemented through the New Hungary Development Plan, co-financed by the European Social Fund and by a grant from National Heart, Lung, and Blood Institute R01HL104126 (to ZB). The authors would like to thank David Durham for the English language edition.

PY - 2013

Y1 - 2013

N2 - Background: Levosimendan and its long-lived metabolite OR-1896 produce vasodilation in different types of vessels by activating ATP-sensitive (KATP) and other potassium channels. Methods: In the present study we applied intravital videomicroscopy to investigate the in situ effects of levosimendan and OR-1896 on the diameters of real resistance arterioles (rat cremaster muscle arterioles with diameters of ~ 20 μm). Results: Levosimendan and OR-1896 induced concentration-dependent (1 nM - 100 μM) dilations to similar extents in these arterioles (maximal dilation from 23 ± 2 to 33 ± 2 μm and from 22 ± 1 to 32 ± 1 μm, respectively). The arteriolar dilations induced by the selective KATP channel opener pinacidil (1 nM - 10 μM) (maximal dilation from 22 ± 4 μm to 35 ± 3 μm) were diminished in the presence of the selective KATP channel blocker - glibenclamide (5 μM) (maximal diameter attained: 22 ± 1 μm). Glibenclamide also counteracted the maximal dilations in response to levosimendan or OR-1896 (to 23 ± 3 μm or 22 ± 5 μm, respectively). Conclusions: In conclusion, this is the first demonstration that levosimendan and OR-1896 elicit arteriolar dilation in vivo, via activation of KATP channels in real resistance vessels in the rat.

AB - Background: Levosimendan and its long-lived metabolite OR-1896 produce vasodilation in different types of vessels by activating ATP-sensitive (KATP) and other potassium channels. Methods: In the present study we applied intravital videomicroscopy to investigate the in situ effects of levosimendan and OR-1896 on the diameters of real resistance arterioles (rat cremaster muscle arterioles with diameters of ~ 20 μm). Results: Levosimendan and OR-1896 induced concentration-dependent (1 nM - 100 μM) dilations to similar extents in these arterioles (maximal dilation from 23 ± 2 to 33 ± 2 μm and from 22 ± 1 to 32 ± 1 μm, respectively). The arteriolar dilations induced by the selective KATP channel opener pinacidil (1 nM - 10 μM) (maximal dilation from 22 ± 4 μm to 35 ± 3 μm) were diminished in the presence of the selective KATP channel blocker - glibenclamide (5 μM) (maximal diameter attained: 22 ± 1 μm). Glibenclamide also counteracted the maximal dilations in response to levosimendan or OR-1896 (to 23 ± 3 μm or 22 ± 5 μm, respectively). Conclusions: In conclusion, this is the first demonstration that levosimendan and OR-1896 elicit arteriolar dilation in vivo, via activation of KATP channels in real resistance vessels in the rat.

KW - Cremaster muscle

KW - Intravital microscopy

KW - KATP channels

KW - Levosimendan

KW - OR-1896

KW - Vasodilation

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U2 - 10.1016/S1734-1140(13)71488-9

DO - 10.1016/S1734-1140(13)71488-9

M3 - Article

C2 - 24399726

AN - SCOPUS:84894178423

SN - 2299-5684

VL - 65

SP - 1304

EP - 1310

JO - Pharmacological Reports

JF - Pharmacological Reports

IS - 5

ER -

Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo

Abstract

Keywords

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