Cardiology Letters 2012, 21(5):388-396
Salutary effects of red palm oil intake on post-ischemic heart recovery and incidence of malignant arrhythmias demonstrated in hypertensive rats
- 1 Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava
- 2 Institute of Experimental Pharmacology and Toxicology, SAS in Bratislava
- 3 The National Cardiovascular Institute in Bratislava, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic
Cardiac connexin-43 (Cx43) channels at the gap junctions play a crucial role in synchronizing the myocardium, allowing electrical and molecular signals propagation amongst cardiomyocytes. Previously we have shown that up-regulation of Cx43 is most likely involved in the antiarrhythmic mechanisms of omega-3 fatty acids. The aim of this study was to explore whether antioxidant rich red palm oil (RPO) may offer protection from malignant arrhythmias and/or attenuate an abnormal myocardial Cx43 expression in spontaneously hypertensive rats (SHR). Untreated hypertensive and age-matched normotensive rats were compared with those supplemented by 200microL/day RPO for 5 weeks. Left ventricular tissue was used for real time PCR analysis, immunoblotting and in situ immunostaining to determine Cx43 gene and protein expression as well as Cx43 distribution. The isolated perfused heart was used to examine post-ischemic reperfusioninduced arrhythmias, electrically inducible ventricular fibrillation (VF) and heart function. Results showed that the expression of Cx43-mRNA and total Cx43 proteins as well as its functional phosphorylated forms were increased and disordered myocardial localization of Cx43 was attenuated in the left ventricles of RPO-fed SHR compared to those untreated. This was associated with suppression of post-ischemic reperfusion-related ventricular tachycardia and electrically-inducible VF, as well as with better post-ischemic heart recovery. However, the treatment dose of RPO caused down-regulation of myocardial Cx43 in normotensive rats, and was associated with poor arrhythmia protection and cardiodepression suggesting overdose. In conclusion, our results indicate that SHR benefit from RPO intake particularly due to better post-ischemic heart recovery and protection from malignant arrhythmias. This cardioprotection can be partially attributed to up-regulation of myocardial Cx43. It appears that consumption of RPO might be salutary in hypertensive individuals, and should be examined by clinicians.
Keywords: hypertensive rats; red palm oil; myocardial connexin43; malignant arrhythmias; heart function
Published: May 1, 2012 Show citation
| ACS | AIP | APA | ASA | Harvard | Chicago | Chicago Notes | IEEE | ISO690 | MLA | NLM | Turabian | Vancouver |
References
- Edem DO. Palm oil: Biochemical, physiological, nutritional, hematological, and toxicological aspects: A review. Plant Foods for Human Nutrition 2002;57:319-341.
Go to original source... - Van Rooyen J, Esterhuyse AJ, Engelbrecht AM, Du Toit EF. Health benefits of a natural carotenoid rich oil: a proposed mechanism of protection against ischaemia/reperfusion injury. Asia Pac J Clin Nutr 2008;17:316-319.
- Esterhuyse AJ, Du Toit EF, Benade AJS, Van Rooyen J. Dietary red palm oil improves reperfusion cardiac function in the isolated perfused rat heart of animals fed a high cholesterol diet. PLEFA 2005;72:153-161.
Go to original source... - Esterhuyse JS, Van Rooyen J, Strijdom H, Bester D, Du Toit EF. Proposed mechanisms for red palm oil induced cardioprotection in a model of hyperlipidaemia in the rat. PLEFA 2006;75:375-384.
Go to original source... - Kruger MJ, Engelbrecht AM, Esterhuyse J, du Toit EF, Van Rooyen J. Dietary red palm oil reduces ischaemia-reperfusion injury in rats fed a hypercholesterolaemic diet. British Journal of Nutrition 2007;97:653-660.
Go to original source... - Engelbrecht AM, Odendaal L, Du Toit EF, Kupai K, Csont T, Ferdinandy P, Van Rooyen J. The effect of dietary red palm oil on the functional recovery of the ischaemic/reperfused rat heart: the involvement of the PI3-kinase signalling pathway. Lipids in Health and Disease 2009;8:18-25.
Go to original source... - Bester DJ, Kupai K, Csont T, Szucs G, Csonka C, Esterhuyse AJ, Ferdinandy P, Van Rooyen J. Dietary red palm oil supplementation reduces myocardial infarct size in an isolated perfused rat heart model. Lipids in Health and Disease 2010;9:64-69.
Go to original source... - Das S, Lekli I, Das M, Szabo G, Varadi J, Juhasz B, Bak I, Nesaretam K, Tosaki A, Powell SR, Das DK. Cardioprotection with palm oil tocotrienols: comparision of different isomers. Am J Physiol Heart Circ Physiol 2008;294:970-978.
Go to original source... - Szucs G, Bester DJ, Kupai K, Csont T, Csonka C, Esterhuyse AJ, Ferdinandy P, Van Rooyen J. Dietary red palm oil supplementation decreases infarct size in cholesterol fed rats. Lipids in Health and Disease 2011;10:103, in press.
Go to original source... - Liu F, Gutstein DE. The Cardiac Gap Junction: A Potential Therapeutic Target in the Treatment of Heart Disease. The Mount Sinai Journal of Medicine 2002;69:421-424.
- Salameh A, Dhein S. Pharmacology of Gap junctions. New pharmacological targets for treatment of arrhythmia, seizure and cancer? Biochim Biophys Acta 2005;1719: 36-58.
Go to original source... - Lin H, Mitasikova M, Dlugosova K, Okruhlicova L, Imanaga I, Ogawa K, Weismann P, Tribulova N. Thyroid hormones suppress epsilon-PKC signalling, down-regulate connexin-43 and increase lethal arrhythmia susceptibility in non-diabetic and diabetic rat hearts. J Physiol Pharmacol 2008;59:271-285.
- Tribulova N, Knezl V, Okruhlicova L, Slezak J. Myocardial gap junctions: targets for novel approaches in the prevention of lifethreatening cardiac arrhythmias. Physiol Res 2008;57:1-13.
Go to original source... - Tribulova N, Seki S, Radosinska J, Kaplan P, Babusikova E, Knezl V, Mochizuki S. Myocardial Ca2+ handling and cell-to-cell coupling, key factors in prevention of sudden cardiac death. Can J Physiol Pharmacol 2009;87:1120-1129.
Go to original source... - Dhein S. Gap junctional channels in cardiovascular system: pharmacological and physiological modulation. Trends Pharmacol Sci 1998;19:229-241.
Go to original source... - Mitasikova M, Smidova S, Macsaliova A, Knezl V, Dlugosova K, Okruhlicova L, Weismann P, Tribulova N. Aged male and female spontaneously hypertensive rats benefit from n-3 polyunsaturated fatty acids supplementation. Physiol Res. 2008;57(Suppl 2):S39-48.
Go to original source... - Bacova B, Radosinska J, Knezl V, Kolenova L, Weismann P, Navarova J, Barancik M, Mitasikova M, Tribulova N. Omega-3 fatty acids and atorvastatin suppress ventricular fibrillation inducibility in hypertrigly-ceridemic rat hearts: implication of intracellular coupling protein, connexin-43. J Physiol Pharmacol 2010;61:717-723.
- Radosinska J, Bacova B, Bernatova I, Navarova J, Zhukovska A, Shysh A, Okruhlicova L, Tribulova N. Myocardial NOS activity and connexin-43 expression in untreated and omega-3 fatty acids-treated spontaneously hypertensive and hereditary hypertriglyceridemic rats. Mol Cell Biochem 2011;347:163-173.
Go to original source... - Bacova B, Radosinska J, Viczenczova C, Knezl V, Dosenko V, Benova T, Navarova J,Gonçalvesova E, Van Rooyen J, Weismann P, Slezak J, Tribulova N. Up-regulation of myocardial connexin-43 in spontaneously hypertensive rats fed red palm oil is most likely implicated in its anti-arrhythmic effects. Can J Physiol Pharmacol 2012;90:1235-1245.
Go to original source... - Kostin S, Rieger M, Dammer S, Hein S, Richter M, Klovekorn WP, Bauer EP, Schaper J. Gap junction remodeling and altered connexin 43 expression in the failing human heart. Mol Cell Biochem 2003;242:135-144.
Go to original source... - Kostin S, Dammer S, Hein S, Klovekorn WP, Bauer EP, Schaper J. Connexin 43 expression and distribution in compensated and decompensated cardiac hypertrophy in patients with aortic stenosis. Cardiovasc Res 2004;62:426-436.
Go to original source... - Tribulova N, Okruhlicova L, Novakova S, Pancza D, Bernatova I, Pechanova O, Weismann P, Manoach M, Seki S, Mochizuki S. Hypertension-related intermyocyte junction remodelling is associated with a higher incidence of low-K(+)-induced lethal arrhythmias in isolated rat heart. Exp Physiol 2002;87:195-205.
Go to original source... - Tribulova N, Okruhlicova L, Varond D, Manoach M, Pechanova O, Bernatova I, Weismann P, Barancik M, Styk J, Slezak J. Structural substrates involved in the development of severe arrhythmias in hypertensive rat and aged guinea pig hearts. In: Signal P, Dixon I, Kirschenbaum L, Dhalla NS. (eds) Cardiac Remodelling and Failure 2002. Boston: Kluwer Academic Publishers; 2002:377398.
Go to original source... - Tribulova N, Okruhlicova L, Imanaga I, Hirosawa N, Ogawa K, Weismann P. Factors involved in the susceptibility of spontaneously hypertensive rats to low K+-induced arrhythmias. Gen Physiol Biophys 2003;22:369-382.
- Conrad CH, Brooks WW, Hayes JA, Sen S, Robinson KG, Bing OHL. Myocardial fibrosis and stiffness with hypertrophy and heart failure in the spontaneously hypertensive rat. Circulation 1995;91:161-170.
Go to original source... - Mancia G, Scopelliti F, Grassi G. Hypertension and heart. Seminars in cardiothoracic and vascular. Anesthesia 2006;10:198-202.
Go to original source... - Dupont E, Matsushita T, Kaba RA, Vozzi C, Coppen SR, Khan N, Kaprielian R, Yacoub MH, Severs NJ. Altered connexin expression in human congestive heart failure. J Mol Cell Cardiol 2001;33:359-371.
Go to original source... - Peters NS, Wit AL. Myocardial architecture and ventricular arrhythmogenesis. Circulation 1998;97:1746-1754.
Go to original source... - Severs NJ, Bruce AF, Dupont E, Rothery S. Remodelling of gap junctions and connexin expression in diseased myocardium. Cardiovascular Res 2008;80;9-19.
Go to original source... - Osim EE, Owu DU, Etta KM. Arterial pressure and lipid profile in rats following chronic ingestion of palm oil diets. Afr J Med Sci 1996;25:335-340.
- Radosinska J, Bacova B, Dosenko V, Lin H, Imanaga I, Tribulova N. Spontaneously diabetic rats in pre-hypertensive stage benefit from omega-3 fatty acids supplementation. J Hypertension 2010;28:292-293.
Go to original source... - Marx N, Froehlich J, Siam L, Ittner J, Wierse G, Schmidt A, Scharnagl H, Hombach V, Koenig W. Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2003;23:283-288.
Go to original source... - Shen Y, Wu H, Wang C, Shao H, Huang H, Jing H, Li D. Simvastatin attenuates cardiopulmonary bypass-induced myocardial inflammatory injury in rats by activating peroxisome proliferator-activated receptor γ. European J Pharmacol 2010;649:255-262.
Go to original source... - Maejima Y, Okada H, Haraguchi G, Onai Y, Kosuge H, Suzuki J, Isobe M. Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma. Laboratory Investigation 2011;91:932-944.
Go to original source... - Bertram JS, Vine AL. Cancer prevention by retinoids and carotenoids: Independent action on a common target. Biochim Biophys Acta 2005;1740:170-178.
Go to original source... - Srisakuldee W, Jeyaraman MM, Nickel BE, Tanguy S, Jiang ZS, Kardami E. Phosphorylation of connexin-43 at serine 262 promotes a cardiac injury-resistant state. Cardiovasc Res 2009;83:672-681.
Go to original source... - Fischer R, Dechend R, Qadri F, Markovic M, Feldt S, Herse F. Dietary n-3 polyunsatur-ated fatty acids and direct renin inhibition improve electrical remodeling in a model of high human renin hypertension. Hypertension 2008;51:540546.
Go to original source...

