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(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels

Authorized Users Only
2018
Authors
Marinko, Marija
Janković, Goran
Nenezić, Dragoslav
Milojević, Predrag
Stojanović, Ivan
Kanjuh, Vladimir
Novaković, Aleksandra
Article (Published version)
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Abstract
In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+, whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+-free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These... results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K-V channels, BKCa channels, and at least partly, K-ATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+-ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.

Keywords:
epicatechin / extracellular calcium / human saphenous vein / intracellular calcium / K+ channels / vasorelaxation
Source:
Phytotherapy Research, 2018, 32, 2, 267-275
Publisher:
  • Wiley, Hoboken
Funding / projects:
  • Investigation of the Effect and Mechanism of Action of Different Vasodilator Substances on the Human Bypass Grafts (RS-175088)

DOI: 10.1002/ptr.5969

ISSN: 0951-418X

PubMed: 29193528

WoS: 000424287300008

Scopus: 2-s2.0-85036571538
[ Google Scholar ]
8
9
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/3191
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Marinko, Marija
AU  - Janković, Goran
AU  - Nenezić, Dragoslav
AU  - Milojević, Predrag
AU  - Stojanović, Ivan
AU  - Kanjuh, Vladimir
AU  - Novaković, Aleksandra
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3191
AB  - In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+, whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+-free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K-V channels, BKCa channels, and at least partly, K-ATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+-ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.
PB  - Wiley, Hoboken
T2  - Phytotherapy Research
T1  - (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels
VL  - 32
IS  - 2
SP  - 267
EP  - 275
DO  - 10.1002/ptr.5969
ER  - 
@article{
author = "Marinko, Marija and Janković, Goran and Nenezić, Dragoslav and Milojević, Predrag and Stojanović, Ivan and Kanjuh, Vladimir and Novaković, Aleksandra",
year = "2018",
abstract = "In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin. Additionally, (-)-epicatechin relaxed contraction induced by 80 mM K+, whereas in the presence of nifedipine produced partial relaxation of HSV rings pre-contracted by phenylephrine. In Ca2+-free solution, (-)-epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, significantly reduced relaxation of HSV produced by (-)-epicatechin. These results demonstrate that (-)-epicatechin produces endothelium-independent relaxation of isolated HSV rings. Vasorelaxation to (-)-epicatechin probably involves activation of 4-aminopyridine- and margatoxin-sensitive K-V channels, BKCa channels, and at least partly, K-ATP channels. In addition, not only the inhibition of extracellular Ca2+ influx, but regulation of the intracellular Ca2+ release, via inositol-trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca2+-ATPase, as well, most likely participate in (-)-epicatechin-induced relaxation of HSV.",
publisher = "Wiley, Hoboken",
journal = "Phytotherapy Research",
title = "(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels",
volume = "32",
number = "2",
pages = "267-275",
doi = "10.1002/ptr.5969"
}
Marinko, M., Janković, G., Nenezić, D., Milojević, P., Stojanović, I., Kanjuh, V.,& Novaković, A.. (2018). (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels. in Phytotherapy Research
Wiley, Hoboken., 32(2), 267-275.
https://doi.org/10.1002/ptr.5969
Marinko M, Janković G, Nenezić D, Milojević P, Stojanović I, Kanjuh V, Novaković A. (-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels. in Phytotherapy Research. 2018;32(2):267-275.
doi:10.1002/ptr.5969 .
Marinko, Marija, Janković, Goran, Nenezić, Dragoslav, Milojević, Predrag, Stojanović, Ivan, Kanjuh, Vladimir, Novaković, Aleksandra, "(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels" in Phytotherapy Research, 32, no. 2 (2018):267-275,
https://doi.org/10.1002/ptr.5969 . .

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