title: Dietary omega-3 fatty acids attenuate myocardial arrhythmogenic factors and propensity of the heart to lethal arrhythmias in a rodent model of human essential hypertension.
abstract: OBJECTIVE
  Hypertension-induced myocardial remodeling is known to be associated with increased risk for malignant arrhythmias and alterations in electrical coupling protein, connexin-43 (Cx43), may be involved. We investigated whether omega-3 fatty acids intake affects abnormalities of Cx43 as well as protein kinase C (PKC) signaling 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, PKCε and PKCδ 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-ε and suppressed pro-apoptotic PKC-δ isoform. Moreover, the omega-3 diet normalized MyHC profiles in SHR at early stage of disease and old nonhypertensive rats, but failed to do so in old SHR at late stage of disease.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aInstitute for Heart Research, Slovak Academy of Sciences bFaculty of Medicine, Institute of Physiology, Comenius University cInstitute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia dFaculty of Science, Department of Physiology, Charles University eInstitute of Physiology, v.v.i., Academy of Sciences of Czech Republic, Prague, Czech Republic fThe National Cardiovascular Institute, Bratislava, Slovakia *Jana Radosinska and Barbara Bacova contributed equally to the writing of the article.
authors.forename: Jana
authors.initials: J
authors.lastname: Radosinska
authors.forename: Barbara
authors.initials: B
authors.lastname: Bacova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Knezl
authors.forename: Tamara
authors.initials: T
authors.lastname: Benova
authors.forename: Jitka
authors.initials: J
authors.lastname: Zurmanova
authors.forename: Tomas
authors.initials: T
authors.lastname: Soukup
authors.forename: Petra
authors.initials: P
authors.lastname: Arnostova
authors.forename: Jan
authors.initials: J
authors.lastname: Slezak
authors.forename: Eva
authors.initials: E
authors.lastname: Gonçalvesova
authors.forename: Narcisa
authors.initials: N
authors.lastname: Tribulova
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000401:mortality; D001794:Blood Pressure; D018031:Connexin 43 / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D005786:Gene Expression Regulation; D006973:Hypertension; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D018031:Connexin 43; D015525:Fatty Acids, Omega-3; D020033:Protein Isoforms; D011493:Protein Kinase C; D018995:Myosin Heavy Chains