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Eugenol interacts with cardiac sodium channel and reduces heart excitability and arrhythmias

2021; Elsevier BV; Volume: 282; Linguagem: Inglês

10.1016/j.lfs.2021.119761

1879-0631

Jorge Lucas Teixeira‐Fonseca, Artur Santos‐Miranda, Joab Barbosa da Silva, Leisiane Pereira Marques, Julliane V. Joviano‐Santos, Paula Idma Chaves Nunes, Danilo Roman‐Campos, Antônio Nei Santana Gondim,

Cardiac electrophysiology and arrhythmias

Eugenol is a natural compound found in the essential oils of many aromatic plants. The compound is used as a local anesthetic because of its inhibitory effect on the voltage-gated Na+ channels (Nav), which are expressed in the nociceptive neurons. Eugenol has shown wide range of activities in the cardiovascular system; most of these activities are attributed to the modulation of voltage-sensitive Ca2+ channels. However, its action on Nav1.5, the main subtype of Nav expressed in the mammalian myocardium, is unknown. The interaction of eugenol with Nav1.5 could also contribute to its antiarrhythmic properties in vitro and ex vivo. We investigated the compound's effect on sodium current (INa) and its possible cardiac antiarrhythmic activity. The effect of eugenol on cardiac contractility was investigated using isolated atrium from guinea pig (for isometric force measurements). The compound's effect on INa was evaluated using human embryonic cell transiently expressing human Nav1.5 and patch-clamp technique. Eugenol caused negative inotropic and chronotropic effects in the atria. In the ex vivo arrhythmia model, eugenol decreased atrial pacing disturbance induced by ouabain. Eugenol reduced the INa in a concentration-dependent manner. Furthermore, the compound left-shifted the stationary inactivation curve, delayed recovery from inactivation of the INa, and preferentially blocked the channel in the inactivated state. Importantly, eugenol was able to attenuate the late sodium current. All these aspects are considered to be antiarrhythmic. Overall, our findings demonstrate that eugenol has antiarrhythmic activity due, at least in part, to its interaction with Nav1.5.