Background and Purpose: Melatonin in addition to regulation of circadian rhythm exhibits antihypertensive, free radicals scavenging and antiarrhythmic effects as we have shown recently. While melatonin deficiency and lower omega-3 index observed in pts suffering from CHD and hypertension as well as in SHR can contribute to disease progression and pro-arrhythmia. Continuous light suppresses melatonin production that is deleterious to the heart. We aimed to explore whether cardioprotective compound Omacor might be beneficial in these conditions.
Design and Methods: Males, age-matched SHR and healthy Wistar rats were housed under standard 12h light/12h dark cycle or exposed to continuous light under 24h light/day for 6 weeks. Half of these rats received Omacor (omega-3 ethyl ester, 25g/kg diet). Left ventricular tissue was analyzed for mRNA of electrical coupling protein, connexin-43 (Cx43), proinflammatory NFkB and iNOS - by using real time PCR, while protein expression of Cx43 and PKCε by western blots. Inducible ventricular fibrillation (VF) was examined using isolated-perfused heart.
Key Results: Comparing to the healthy rats plasma levels of melatonin and omega-3 index were lower in SHR. Continuous light caused mild elevation of BP in healthy rats and enhanced it in SHR and also decreased threshold to induce VF in both groups comparing to the rats under normal light cycle. Myocardial Cx43 mRNA level was not altered but Cx43 protein and its functional phosphorylated forms (which affect electrical coupling) were decreased in SHR due to continuous light and partially restored by Omacor. Treatment with Omacor increased threshold for VF and it was associated with attenuation of continuous light-induced increase of myocardial iNOS and proinflammatory NFkB gene expression that down-regulates Cx43.
Conclusions: Findings indicate that continuous light itself impairs Cx43 channels-mediated cardiac cell-to-cell coupling that may increase propensity of SHR to malignant arrhythmias. These adverse effects can be, in part, eliminated by treatment with Omacor.