Official journal of the Slovak Society of Cardiology,
Slovak Society of Hypertension and Slovak Association for Cardiac Arrhythmias

Cardiology Letters 2014, 23(1):10-16

Omega-3 polyunsaturated fatty acids affect arrhythmogenic factors and attenuate susceptibility of the heart to malignant arrhythmias in an experimental model of human essential hypertension

Radošinská J1, 2, Bačová B1, Knezl V3, Beňová T1, Zurmanová J4, Soukup T5, Arnoštová P4, Slezák J1, Gonçalvesová E6, Tribulová N1
1 Ústav pre výskum srdca SAV, Bratislava, Slovenská republika
2 Fyziologický ústav LF UK, Bratislava, Slovenská republika
3 Ústav experimentálnej farmakológie a toxikológie SAV, Bratislava, Slovenská republika
4 Katedry fyziologie Přírodovědecké fakulta Univerzita Karlovy v Praze, Česká republika
5 Fyziologický ústav AV ČR, Praha, Česká republika
6 Národný ústav srdcových a cievnych chorôb, Bratislava, Slovenská republika

Objective: Hypertension-induced myocardial remodelling is known to be associated with increased risk of malignant arrhythmias and alterations in electrical coupling protein, connexin-43 (Cx43), may be involved in the pathogenesis. We investigated whether omega-3 fatty acids intake affects abnormalities of Cx43 as well as protein kinase C (PKC) signalling and myosin heavy chain (MyHC) profile at the early and late stage of hypertension in the context of the heart's susceptibility to ventricular fibrillation and ability to restore sinus rhythm.

Methods: Untreated young and old male spontaneously hypertensive rats (SHRs) and age-matched normotensive rats were compared with animals supplemented by omega-3 (eicosapentaneoic acid + docosahexaneoic acid, 200 mg/kg body weight/day) for 2 months. Left ventricular tissues were taken for examination of subcellular integrity of gap junctions, Cx43 mRNA and protein expression, PKC-epsilon and PKC-delta as well as MyHC determination. Electrically inducible ventricular fibrillation and sinus rhythm restoration (SRR) were examined on Langedorff-perfused heart preparation.

Results: Omega-3 intake significantly reduced cardiovascular risk factors, suppressed inducible ventricular fibrillation, and facilitated SRR in hypertensive rats. Supplementation attenuated lateralization and internalization of Cx43, suppressed elevated Cx43 mRNA, enhanced total Cx43 protein expression and/or expression of its functional phosphorylated forms as well as the expression of cardioprotective PKC-epsilon and suppressed proapoptotic PKC-delta isoform. Moreover, the omega-3 diet normalized MyHC profiles in SHR at early stage of disease and old nonhypertensive rats.

Conclusion: Findings suggest that amelioration of myocardial Cx43-related abnormalities, positive modulation of PKC pathways, and normalization of MyHC can significantly contribute to the antiarrhythmic effects of omega-3 in rat model mimicking human essential hypertension. Our results support the prophylactic use of omega-3 to minimize cardiovascular risk and sudden arrhythmic death.

Keywords: spontaneously hypertensive rat; gap-junction; connexin-43; omega-3 polyunsaturated acids; malignant arrhythmias

Published: January 1, 2014  Show citation

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Radošinská J, Bačová B, Knezl V, Beňová T, Zurmanová J, Soukup T, et al.. Omega-3 polyunsaturated fatty acids affect arrhythmogenic factors and attenuate susceptibility of the heart to malignant arrhythmias in an experimental model of human essential hypertension. Cardiology Letters. 2014;23(1):10-16.
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