(−)‐Epicatechin‐induced relaxation of isolated human saphenous vein: Roles of K+ and Ca2+ channels |
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| Authors: | Marija Marinko Goran Jankovic Dragoslav Nenezic Predrag Milojevic Ivan Stojanovic Vladimir Kanjuh Aleksandra Novakovic |
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| Affiliation: | 1. Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia;2. Faculty of Medicine, University of Belgrade, Belgrade, Serbia;3. Institute for Cardiovascular Diseases “Dedinje”, Belgrade, Serbia;4. Academy of Sciences and Arts, Belgrade, Serbia |
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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 KV channels, BKCa channels, and at least partly, KATP 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. |
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| Keywords: | epicatechin extracellular calcium human saphenous vein intracellular calcium K+ channels vasorelaxation |
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