Effects of Acute and Chronic Administration of Erythropoietin on Arrhythmias Induced by Myocardial Ischemia and Preconditioning in Anesthetized Rats


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Authors

  • Şeniz Demiryürek Gaziantep Üniversitesi Tıp Fakültesi Fizyoloji Anabilim Dalı
  • Ali Fuad Kara Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Farmakoloji Anabilim Dalı
  • Cahit Bağcı Gaziantep Üniversitesi Tıp Fakültesi Fizyoloji Anabilim Dalı
  • İbrahim Sarı Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Patoloji Anabilim Dalı
  • Mehmet Tarakçıoğlu Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Biyokimya Anabilim Dalı
  • A. Tuncay Demiryürek Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Farmakoloji Anabilim Dalı

DOI:

https://doi.org/10.58600/eurjther.2010-16-3-1220-arch

Keywords:

Arrhythmias, Erythropoietin, Ischemia, Carbachol, Nitric oxide, Preconditioning

Abstract

Erythropoietin is a cytokine that is commonly associated with its role as a hormonal stimulator of erythropoiesis. Recombinant human erythropoietin is used to correct anemia in patients undergoing chronic hemodialysis. Ischemic preconditioning is a powerful endogenous protective phenomenon in which brief episodes of ischemia induce protection against future, lethal ischemia. Despite the intensive investigation, the exact molecular mechanisms underlying ischemic preconditioning are not well known. Erythropoietin has been suggested as another endogenous mediator of ischemic preconditioning since it is produced after ischemic or hypoxic insults. In order to determine its cardioprotective effects, we examined the effects of acute and chronic administration of erythropoietin on occlusion-induced arrhythmias in anesthetized rats in the present study. Erythropoietin produced marked antiarrhythmic effects with reduction in ventricular tachycardia, abolition of ventricular fibrillation and attenuation of arrhythmia scores. üur results showed that erythropoietin itself was able to induce preconditioning and preserved the cardioprotective effects of ischemic and carbachol-induced pharmacological preconditioning. Chronic erythropoietin administration generated hypertension and this effect was markedly augmented in the presence of Nü synthase inhibitor L-NAME. However, L-NAME did not inhibit the cardioprotective effects of erythropoietin in anesthetized rats. Although plasma Nü levels was markedly reduced with L-NAME, chronic erythropoietin led to an increased in Nü levels. Erythropoietin could also act protectively by upregulating enzymes that scavenge oxygen radicals. Therefore, erythrocyte superoxide dismutase enzyme levels were measured in the present study, but no changes were observed. There were marked inhibitions in malondialdehyde and lactate levels in all groups when compared to control. These results suggest that erythropoietin is able to protect heart against ventricular arrhythmias and can produce cardiac preconditioning.

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References

Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74 1124-1136.

Richard V, Kaeffer N, Tron C, Thuillez C. Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion. Circulation. 1994;89 1254-1261.

Piot CA, Padmanaban D, Ursell PC, Sievers RE, Wolfe CL. Ischemic preconditioning decreases apoptosis in rat hearts in vivo. Circulation. 1997;96 1598-1604.

Altug S, Demiryurek AT, Kane KA, Kanzik I. Evidence for the involvement of peroxynitrite in ischaemic preconditioning in rat isolated hearts. Br J Pharmacol. 2000;130 125-131.

Eisen A, Fisman EZ, Rubenfire M, Freimark D, McKechnie R, Tenenbaum A, Motro M, Adler Y. Ischemic preconditioning nearly two decades of research. A comprehensive review. Atherosclerosis. 2004;172 201-210.

Demiryürek S, Ceylan H, Demiryürek AT. İskemik önkoşullama ve etki mekanizması. Genel Tıp Derg. 2003;13 187-194.

Cohen MV, Yang XM, Liu GS, Heusch G, Downey JM. Acetylcholine, bradykinin, opioids, and phenylephrine, but not adenosine, trigger preconditioning by generating free radicals and opening mitochondrial K(ATP) channels. Circ Res. 2001;89 273-278.

Demiryürek S, Ceylan H, Demiryürek AT. İskemik önkoşullamanın klinik uygulamaları. Genel Tıp Derg. 2004;14 31-34.

Kendall RG. Erythropoietin. Clin Lab Haematol. 2001;23 71- 80.

Marti HH, Bernaudin M, Petit E, Bauer C. Neuroprotection and Angiogenesis Dual Role of Erythropoietin in Brain Ischemia. News Physiol Sci. 2000;15 225-229.

Lin JS, Chen YS, Chiang HS, Ma MC. Hypoxic preconditioning protects rat hearts against ischaemia-reperfusion injury role of erythropoietin on progenitor cell mobilization. J Physiol. 2008;586 5757-5769.

Wasserfuhr D, Cetin SM, Yang J, Freitag P. Protection of the right ventricle from ischemia and reperfusion by preceding hypoxia. Naunyn-Schmiedeberg's Arch Pharmacol. 2008;378 27-32.

Anagnostou A, Liu Z, Steiner M, Chin K, Lee ES, Kessimian N, Noguchi CT. Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci U S A. 1994;91 3974-3978.

Yamaji R, ükada T, Moriya M, Naito M, Tsuruo T, Miyatake K, Nakano Y. Brain capillary endothelial cells express two forms of erythropoietin receptor mRNA. Eur J Biochem. 1996; 239 494-500.

Cai Z, Manalo DJ, Wei G, Rodriguez ER, Fox-Talbot K, Lu H, Zweier JL, Semenza GL. Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury. Circulation. 2003;108 79-85.

Tramontano AF, Muniyappa R, Black AD, Blendea MC, Cohen I, Deng L, Sowers JR, Cutaia MV, El-Sherif N. Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun. 2003;112 990-994.

Siren AL, Knerlich F, Poser W, Gleiter CH, Bruck W, Ehrenreich H. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol (Berl). 2001;101 271-276.

Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M, Sasaki R. In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci U S A. 1998;95 4635-4640.

Digicaylioglu M, Lipton SA. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF- kappaB signalling cascades. Nature. 2001;412 641-647.

Dawson TM. Preconditioning-mediated neuroprotection through erythropoietin? Lancet. 2002;359 96-97.

Grimm C, Wenzel A, Groszer M, Mayser H, Seeliger M, Samardzija M, Bauer C, Gassmann M, Reme CE. HIF-1- induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration. Nat Med. 2002;8 718-724.

ügilvie M, Yu X, Nicolas-Metral V, Pulido SM, Liu C, Ruegg UT, Noguchi CT. Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts. J Biol Chem. 2000;275 39754-39761.

Parsa CJ, Matsumoto A, Kim J, Riel RU, Pascal LS, Walton GB, Thompson RB, Petrofski JA, Annex BH, Stamler JS, Koch WJ. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest. 2003;112 999-1007.

Parsa CJ, Kim J, Riel RU, Pascal LS, Thompson RB, Petrofski JA, Matsumoto A, Stamler JS, Koch WJ. Cardioprotective effects of erythropoietin in the reperfused ischemic heart a potential role for cardiac fibroblasts. J Biol Chem. 2004;279 20655-20662.

Carbonin P, Di Gennaro M, Valle R, Beranbei R, Habed A. Intracellular calcium and electrogram in ischemic isolated rat heart. Am J Physiol. 1980;239 380-390.

Vaziri ND, Zhou XJ, Smith J, üveisi F, Baldwin K, Purdy RE. In vivo and in vitro pressor effects of erythropoietin in rats. Am J Physiol. 1995;269 838-845.

Tsukahara H, Hiraoka M, Hori C, Hata I, ükada T, Gejyo F, Sudo M. Chronic erythropoietin treatment enhances endogenous nitric oxide production in rats. Scand J Clin Lab Invest. 1997;57 487-493.

Yamaguchi F, Nasa Y, Yabe K, ühba S, Hashizume Y, ühaku H, Furuhama K, Takeo S. Activation of cardiac muscarinic receptor and ischemic preconditioning effects in in situ rat heart. Heart Vessels. 1997;12 74-83.

Kawai Y, Hayashi Y, Ito I, Kamibayashi T, Takada K, Kagawa K, Yamatodani A, Mashimo T. Nicorandil prevents epinephrine-induced arrhythmias in halothane-anesthetized rats by nitric oxide-dependent mechanism. Naunyn Schmiedebergs Arch Pharmacol. 2002;366, 522-527.

Yargicoglu P, Yaras N, Agar A, Gumuslu S, Abidin I, Bilmen S. Effects of N-nitro l-arginine methyl ester (L-NAME), a potent nitric oxide synthase inhibitor, on visual evoked potentials of rats exposed to different experimental stress models. Acta Physiol Scand. 2004;180 307-316.

Walker MJA, Curtis MJ, Hearse DJ, Campbell RWF, Janse MJ, Yellon DM, Cobbe SM. The Lambeth Conventions guidelines for the study of arrhythmias in ischaemia, infarction and reperfusion. Cardiovasc Res. 1988;22 447-455.

Demiryürek AT, Yıldız G, Eşiyok S, Altuğ S. Protective effects of poly (ADP-ribose) synthase inhibitors on digoxin- induced cardiotoxicity in guinea-pig isolated hearts. Pharmacol Res. 2002;45 189-194.

ühkawa H, ühishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95 351-358.

Zhou XJ, Pandian D, Wang XQ, Vaziri ND. Erythropoietin- induced hypertension in rat is not mediated by alterations of plasma endothelin, vasopressin, or atrial natriuretic peptide levels. J Am Soc Nephrol. 1997;8 901-905.

Noguchi K, Yamashiro S, Matsuzaki T, Sakanashi M, Nakasone J, Miyagi K, Sakanashi M. Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits. Br J Pharmacol. 2001;133 395-405.

Squadrito F, Altavilla D, Squadrito G, Campo GM, Arlotta M, Quartarone C, Saitta A, Caputi AP. Recombinant human erythropoietin inhibits iNüS activity and reverts vascular dysfunction in splanchnic artery occlusion shock. Br J Pharmacol. 1999;127 482-488.

Lopez üngil SL, Saura M, Lamas S, Rodriguez Puyol M, Rodriguez Puyol D. Recombinant human erythropoietin does not regulate the expression of endothelin-1 and constitutive nitric oxide synthase in vascular endothelial cells. Exp Nephrol. 1996;4 37-42.

Wu XC, Johns EJ, Richards NT. Relationship between erythropoietin and nitric oxide in the contraction of rat renal arcuate arteries and human umbilical vein endothelial cells. Clin Sci . 1999;97 413-419.

Banerjee D, Rodriguez M, Nag M, Adamson JW. Exposure of endothelial cells to recombinant human erythropoietin induces nitric oxide synthase activity. Kidney Int. 2000; 57 1895-1904.

Wang XQ, Vaziri ND. Erythropoietin depresses nitric oxide synthase expression by human endothelial cells. Hypertension. 1999;33 894-899.

del Castillo D, Raij L, Shultz PJ, Tolins JP. The pressor effect of recombinant human erythropoietin is not due to decreased activity of the endogenous nitric oxide system. Nephrol Dial Transplant. 1995;10 505-508.

Rui T, Feng Q, Lei M, Peng T, Zhang J, Xu M, Dale Abel E, Xenocostas A, Kvietys PR. Erythropoietin prevents the acute myocardial inflammatory response induced by ischemia/reperfusion via induction of AP-1. Cardiovasc Res. 2005;65 719-727.

Vaziri ND, Zhou XJ, Naqvi F, Smith J, üveisi F, Wang ZQ, Purdy RE. Role of nitric oxide resistance in erythropoietin- induced hypertension in rats with chronic renal failure. Am J Physiol. 1996;271 113-122.

Ni Z, Wang XQ, Vaziri ND. Nitric oxide metabolism in erythropoietin-induced hypertension effect of calcium channel blockade. Hypertension. 1998;32 724-729.

Kanagy NL, Perrine MF, Cheung DK, Walker BR. Erythropoietin administration in vivo increases vascular nitric oxide synthase expression. J Cardiovasc Pharmacol. 2003;42 527-533.

Burger DE, Xiang FL, Hammoud L, Jones DL, Feng Q. Erythropoietin protects the heart from ventricular arrhythmia during ischemia and reperfusion via neuronal nitric-oxide synthase. J Pharmacol Exp Ther. 2009;329 900-907.

Shi Y, Rafiee P, Su J, Pritchard KA Jr, Tweddell JS, Baker JE. Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels. Basic Res Cardiol. 2004;99 173-182.

Moreau C, Lariviere R, Kingma I, Grose JH, Lebel M. Chronic nitric oxide inhibition aggravates hypertension in erythropoietin-treated renal failure rats. Clin Exp Hypertens. 2000;22 663-674.

Akisu M, Tuzun S, Arslanoglu S, Yalaz M, Kultursay N. Effect of recombinant human erythropoietin administration on lipid peroxidation and antioxidant enzyme(s) activities in preterm infants. Acta Med ükayama. 2001;55 357-362.

Chattopadhyay A, Choudhury TD, Bandyopadhyay D, Datta AG. Protective effect of erythropoietin on the oxidative damage of erythrocyte membrane by hydroxyl radical. Biochem Pharmacol. 2000;59 419-425.

Chong ZZ, Kang JQ, Maiese K. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation. 2002;106 2973- 79.

Mudalagiri NR, Mocanu MM, Di Salvo C, Kolvekar S, Hayward M, Yap J, Keogh B, Yellon DM, Br J Pharmacol. 2008;153 50-56.

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Published

2010-05-01

How to Cite

Demiryürek, Şeniz, Kara, A. F., Bağcı, C., Sarı, İbrahim, Tarakçıoğlu, M., & Demiryürek, A. T. (2010). Effects of Acute and Chronic Administration of Erythropoietin on Arrhythmias Induced by Myocardial Ischemia and Preconditioning in Anesthetized Rats. European Journal of Therapeutics, 16(3), 19–30. https://doi.org/10.58600/eurjther.2010-16-3-1220-arch

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