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(−)‐Epicatechin‐induced relaxation of isolated human saphenous vein: Roles of K + and Ca 2+ channels
Author(s) -
Marinko Marija,
Jankovic Goran,
Nenezic Dragoslav,
Milojevic Predrag,
Stojanovic Ivan,
Kanjuh Vladimir,
Novakovic Aleksandra
Publication year - 2018
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5969
Subject(s) - iberiotoxin , thapsigargin , phenylephrine , chemistry , glibenclamide , contraction (grammar) , tetraethylammonium , biophysics , caffeine , channel blocker , potassium channel , endoplasmic reticulum , endocrinology , calcium , biochemistry , biology , potassium , organic chemistry , blood pressure , diabetes mellitus
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 Ca 2+ ‐free solution, (−)‐epicatechin relaxed contraction induced by phenylephrine, but had no effect on contraction induced by caffeine. A sarcoplasmic reticulum Ca 2+ ‐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, BK Ca channels, and at least partly, K ATP channels. In addition, not only the inhibition of extracellular Ca 2+ influx, but regulation of the intracellular Ca 2+ release, via inositol‐trisphosphate receptors and reuptake into sarcoplasmic reticulum, via stimulation of Ca 2+ ‐ATPase, as well, most likely participate in (−)‐epicatechin‐induced relaxation of HSV.