(-)-Epicatechin-induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels
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2018
Authors
Marinko, Marija
Janković, Goran
Nenezić, Dragoslav
Milojević, Predrag
Stojanović, Ivan
Kanjuh, Vladimir
Novaković, Aleksandra

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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 / vasorelaxationSource:
Phytotherapy Research, 2018, 32, 2, 267-275Publisher:
- Wiley, Hoboken
Funding / projects:
DOI: 10.1002/ptr.5969
ISSN: 0951-418X
PubMed: 29193528
WoS: 000424287300008
Scopus: 2-s2.0-85036571538
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PharmacyTY - 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 . .