Up-Regulation of Myocardial Connexin-43 and Pkce Is Most Likely Involved in Cardioprotective-Antiarrhythmic Effects of Omega-3 Fatty Acids in Old Hypertensive Rats: Pp.29.162

Background: Hypertension-induced myocardial remodelling contributes to both heart failure and occurrence of life-threatening arrhythmias. Clinical studies showed that omega-3 polyunsaturated fatty acids (omega-3) reduce the incidence of cardiovascular diseases and sudden cardiac death. However, mechanisms are not fully elucidated. Myocardial connexin (Cx) channels at the gap junctions ensure electrical coupling and cardiac synchronisation. The aim of this study was to investigate whether omega-3 affect distribution, expression and/or phosphorylation of Cx-43 in aged spontaneously hypertensive rats (SHR). Myocardial ultrastructure and susceptibility of the heart to ventricular fibrillation (VF) were examined as well. Design and Methods: Male, 14-months-old SHR and non-hypertensive Lewis rats (NLR) were fed with omega-3 (Vesteralens, Norway, 40 mg/day/2mth) and compared with untreated. Blood pressure was registered and left ventricular tissues were processed for ‘in situ’ immunodetection of Cx43 and electron microscopy. Western blotting was used to assess total Cx43 expression, its phosphorylation status and expression of protein kinases C (which phopshorylate Cx43). Susceptibility to electrically-induced VF was tested using Langendorff isolated heart model. Results showed that omega-3 supplementation led to a significant decline of blood pressure in SHR and reduced incidence of VF despite myocardial fibrosis, hypertrophy and abnormal Cx43 distribution (remodelling) were not eliminated but integrity of the cardiomyocytes and their junctions were improved. Total myocardial Cx43 expression and its phosphorylated forms were markedly decreased in SHR, while significantly increased due to omega-3. It was accompanied by enhanced PKCe expression different to its suppression in untreated SHR. Conclusions: Findings indicate that up-regulation of myocardial connexin-43 and PKC-e is most likely involved in the mechanisms of antiarrhytmic effects of omega-3 fatty acids in old hypertensive rats. Results challenge to know a possible beneficial effects of omega-3 fatty acids supplementation in patients suffering from hypertension.