Epicatechin’s cardiovascular protective effects are mediated via opioid receptors and nitric oxide

  • Kirsty MacRae
  • Kylie Connolly
  • Rebecca Vella
  • Andrew Fenning
Original Contribution



Cardiovascular disease is the leading cause of mortality globally. Epicatechin has previously been shown to improve vascular responses and possess cardioprotective properties. However, the mechanisms underpinning these cardiotropic outcomes remain unknown. The aim of this study was to further identify epicatechin’s mechanism of action in the cardiovasculature.


The effects of epicatechin on isolated rat conduit arteries, resistance vessels and cardiac electrophysiology were investigated on resting tension and precontracted vessels and cardiac action potential parameters, both in the presence and in the absence of various antagonists.


At resting tension, epicatechin alone did not affect the vasoreactivity of either conduit or resistance vessels. In noradrenaline pre-contracted thoracic aortic arteries and potassium chloride pre-contracted mesenteric vessels, epicatechin (10−9–10−4 M) induced significant vasorelaxation. The addition of naloxone (10−5 M), NG-nitro-L-arginine methyl ester (10−5M), 4-aminopyridine (5 mM) and verapamil (10−5 M) attenuated epicatechin-mediated vasorelaxation. No change in epicatechin-mediated vasorelaxation was observed with the addition of atropine (10−5 M). Epicatechin significantly improved cardiac electrophysiology by reducing the resting membrane potential, action potential amplitude and force of contraction that was mitigated following the addition of naloxone (10−5 M). Epicatechin significantly decreased the action potential duration at 20, 50 and 90% duration and time to 90% relaxation of force that was unchanged following the addition of naloxone (10−5 M).


These findings suggest epicatechin’s vascular responses and cardioprotective effects are mediated through opioid receptors, nitric oxide, potassium channel and calcium channel activation and highlight the importance of the endothelium/nitric oxide in epicatechin mediated vasorelaxation.


Cardiovascular disease Epicatechin Flavonoids Nitric oxide Opioid receptors 



The authors would like to thank Kieran Behan (Rockhampton Base Hospital, Rockhampton, Queensland, Australia) for providing the naloxone used in this study and the Office of Research Services, CQUniversity for providing the funding for this study.

Compliance with ethical standards

Ethical standards

Ethical clearance for this Project was obtained from the Animal Ethics Committee of Central Queensland University (AEC# A14/11-321) and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The manuscript does not contain clinical studies or patient data.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kirsty MacRae
    • 1
  • Kylie Connolly
    • 1
  • Rebecca Vella
    • 1
  • Andrew Fenning
    • 1
  1. 1.School of Health, Medical and Applied SciencesCQUniversityNorth RockhamptonAustralia

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