Cardiology Letters 2015, 24(2):60-69

The role of melatonin in protecting the heart against malignant arrhythmias

Beňová T¹, Viczenczová C¹, Radošinská J^{1, 2}, Szeiffová Bačová B¹, Knezl V³, Dosenko V⁴, Weismann P⁵, Zeman M⁶, Navarová J³, Tribulová N¹

¹ Ústav pre výskum srdca, SAV, Bratislava

² Fyziologický ústav Lekárská fakulta UK v Bratislave

³ Ústav experimentálnej farmakológie a toxikológie SAV, Bratislava

⁴ Fyziologický ústav Bogomoletz, Kyjev, Ukrajina

⁵ Anatomický ústav Lekárská Fakulty UK, Bratislava

⁶ Prírodovedecká fakulta UK, Bratislava, Slovenská republika

Objectives: It is very well known from experimental as well as clinical studies that the pineal hormone, melatonin, which regulates circadian rhythms, exhibits cardioprotective effects. The goal of the study was to confirm our hypothesis and to explore the antiarrhythmic effects of the supplementation of melatonin in hypertensive and normotensive rats. Additionally, we aimed to discover the supposed mechanisms of these effects, i.e. the cooperation of cardiac connexin-43 (Cx43), which provides electrical signal transmission, and the effect of protein kinase C epsilon (PKCε), which modulates Cx43.

Methods: We used spontaneously hypertensive rats (SHR, n=24) and normotensive Wistar rats (n=24) fed with a standard laboratory diet and situated in standard laboratory light conditions (12 hours light/12 hours dark). Melatonin (40 µg/mL) was administered daily to drinking water during the night phase for a duration of five weeks to both hypertensive (n=12) and normotensive (n=12) rats. Systolic blood pressure, biometrical and biochemical parameters were registered at the beginning and at the end of the experiment. The tissue from the left ventricle was used for the analysis of Cx43 and PKCε. The threshold to induce ventricular fibrillation (VF) was tested on an isolated pefused heart setup.

Results: At the onset, plasma levels of melatonin were lower in hypertensive compared to normotensive rats. The exogenous supplementation of melatonin to hypertensive rats resulted in increased plasma levels of melatonin. Moreover, melatonin decreased blood pressure and normalized the level of triglycerides in hypertensive rats, while it decreased body weight and visceral fat in normotensive rats. Heart and left ventricular weight were not affected by melatonin in any of the rat groups. The threshold to induce VF was significantly lower in hypertensive compared to the normotensive rats and significantly increased after the treatment with melatonin. Increased gene expression of Cx43 as well as the expression of Cx43 protein and that of its phosphorylated (functional) forms in the heart of rats exposed to melatonin were also found. Furthermore, the application of melatonin reduced abnormal (proarrythmogenic) myocardial localization of Cx43 in hypertensive rats and increased the expression of PKCε in both groups.

Keywords: hypertensive rats; melatonin; connexin-43; ventricular fibrillation

Published: February 1, 2015  Show citation