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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1304-1310
Number of pages7
JournalPharmacological Reports
Volume65
Issue number5
DOIs
StatePublished - 2013

Fingerprint

KATP Channels
Dilatation
Arteries
Arterioles
Glyburide
Pinacidil
Abdominal Muscles
Video Microscopy
Potassium Channels
Vasodilation
simendan
N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide
Adenosine Triphosphate

Keywords

  • Cremaster muscle
  • Intravital microscopy
  • KATP channels
  • Levosimendan
  • OR-1896
  • Vasodilation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo. / Gödény, Ildikó; Pollesello, Piero; Édes, István; Papp, Zoltán; Bagi, Zsolt.

In: Pharmacological Reports, Vol. 65, No. 5, 2013, p. 1304-1310.

Research output: Contribution to journalArticle

Gödény, Ildikó ; Pollesello, Piero ; Édes, István ; Papp, Zoltán ; Bagi, Zsolt. / Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo. In: Pharmacological Reports. 2013 ; Vol. 65, No. 5. pp. 1304-1310.
@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",
year = "2013",
doi = "10.1016/S1734-1140(13)71488-9",
language = "English (US)",
volume = "65",
pages = "1304--1310",
journal = "Pharmacological Reports",
issn = "1734-1140",
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

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

UR - http://www.scopus.com/inward/record.url?scp=84894178423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894178423&partnerID=8YFLogxK

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

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

M3 - Article

C2 - 24399726

AN - SCOPUS:84894178423

VL - 65

SP - 1304

EP - 1310

JO - Pharmacological Reports

JF - Pharmacological Reports

SN - 1734-1140

IS - 5

ER -