(-)-Carvone Modulates Intracellular Calcium Signaling with Antiarrhythmic Action in Rat Hearts.

Autor:	Silva GBAD; Universidade Federal de Sergipe, São Cristóvão, SE - Brasil., Souza DS; Universidade Federal de Sergipe, São Cristóvão, SE - Brasil., Menezes-Filho JER; Universidade Federal de Sergipe, São Cristóvão, SE - Brasil., Silva-Neto JAD; Universidade Federal de Sergipe, São Cristóvão, SE - Brasil., Cruz JDS; Universidade Federal de Minas Gerais - Instituto de Ciências Biológicas, Belo Horizonte, MG - Brasil., Roman-Campos DR; Universidade Federal de São Paulo, São Paulo, SP - Brasil., Quintans-Júnior LJ; Universidade Federal de Sergipe, São Cristóvão, SE - Brasil., Vasconcelos CML; Universidade Federal de Sergipe, São Cristóvão, SE - Brasil.
Jazyk:	English; Portuguese
Zdroj:	Arquivos brasileiros de cardiologia [Arq Bras Cardiol] 2022 Aug; Vol. 119 (2), pp. 294-304.
DOI:	10.36660/abc.20210499
Abstrakt:	Background: (-)-Carvone is a monoterpene found in essential oils with antioxidant and anti-inflammatory activity. Objective: The aim of this paper was to analyze the antiarrhythmic property of (-)-carvone in the rat heart and its effects on the intracellular Ca2+ signaling. Methods: The effects of (-)-carvone were evaluated on the ventricular (0.5 mM) and atrial contractility (0.01 - 4 mM) and on electrocardiogram (0.5 mM). Fractional shortening, L-type calcium current (ICa,L) and Ca2+ signaling were measured in the isolated cardiomyocyte (0.5 mM). Antiarrhythmic effect was evaluated in arrhythmia model induced by calcium overload (0.5 mM) (n = 5). P < 0.05 was used as the significance level. Results: In the atrium, (-)-carvone evoked negative inotropism that was concentration-dependent (EC50 0.44 ± 0.11 mM) and decreased the positive inotropism evoked by CaCl2 (0.1 to 8.0 mM) or BAY K8644 (5 to 500 nM), an agonist of L-type Ca2+ channel. In isolated heart, (-)-carvone (0.5 mM) promoted reduction of ventricular contractility (73%) and heart rate (46%), increased PRi (30.7%, time from the onset of the P wave until the R wave) and QTc (9.2%, a measure of the depolarization and repolarization of the ventricles) without changing the QRS complex duration. (-)-Carvone decreased the fractional shortening (61%), ICa,L (79%) and Ca2+ intracellular transient (38%). Furthermore, (-)-carvone showed antiarrhythmic action, verified by decrease of the arrhythmia score (85%) and occurrence of ventricular fibrillation. Conclusion: (-)-Carvone decreases Ca2+ entry through L-type Ca2+ channels, reducing the cardiac contractility and intracellular Ca2+, and, therefore, presenting promising antiarrhythmic activity in the rat hearts.
Databáze:	MEDLINE
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