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

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: 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. Methods: 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. Results: 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), N G -nitro-L-arginine methyl ester (10 −5 M), 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). Conclusions: 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.