Chapters authored
Myocardial Connexin-43 is Implicated in the Prevention of Malignant Arrhythmia in Rats Suffering from Essential Hypertension
Gap-junction connexin (Cx) channels are important determinants of myocardial conduction and synchronization that is crucial for heart function. Hypertension-induced structural remodeling is associated with an increased risk of life-threatening arrhythmias and heart failure in both humans and experimental animals. Recent studies suggest that abnormal distribution and/or downregulation of Cx43 accompanied with altered protein kinase C (PKC)ε signaling in spontaneously hypertensive rats were linked with increased propensity to ventricular fibrillation compared to normotensive rats. By contrast, the long-term treatment of hypertensive rats with cardioprotective compounds such as melatonin, omega-3 fatty acids, or red palm oil resulted in protection from lethal arrhythmia. Their antiarrhythmic effect was attributed to the attenuation of abnormal Cx43 topology and modulation of Cx43 mRNA as well as protein expression and its functional phosphorylated forms. The latter might be attributed to upregulation of PKCε. It appears that maladaptive consequences of hypertension resulting in abnormal myocardial distribution of Cx43 and its downregulation can contribute to arrhythmogenesis and occurrence of malignant arrhythmias. On the other hand, the attenuation of myocardial Cx43 abnormalities by treatment with melatonin, omega-3 fatty acids, or red palm oil confers arrhythmia protection in rodent model of essential hypertension. Findings uncover novel mechanisms of cardioprotective effects of melatonin, omega-3 fatty acids, and red palm oil. Well-designed clinical trials are needed to explore antiarrhythmic potential of these compounds in human essential hypertension.
Part of the book: Update on Essential Hypertension