Effects of the calcium sensitizer OR-1896, a metabolite of levosimendan, on post-infarct heart failure and cardiac remodelling in diabetic Goto-Kakizaki rats

British Journal of Pharmacology

Volumn 160, Issue 1, 2010, Pages 142-152

  Louhelainen, Marjut ^a   Merasto, Saara ^a   Finckenberg, Piet ^a   Vahtola, Erik ^a   Kaheinen, Petri ^a   Levijoki, Jouko ^b   Mervaala, Eero ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

^b ORION CORPORATION   (Finland)

Author keywords

Calcium sensitizer; Cardiac remodelling; Heart failure; Senescence

Indexed keywords

ATRIAL NATRIURETIC FACTOR; CONNECTIVE TISSUE GROWTH FACTOR; CYCLIN DEPENDENT KINASE INHIBITOR 2A; LEVOSIMENDAN; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; N [4 (1,4,5,6 TETRAHYDRO 4 METHYL 6 OXO 3 PYRIDAZINYL)PHENYL]ACETAMIDE; PROTEIN P19;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARDITIS; CONTROLLED STUDY; DISEASE MARKER; DRUG EFFICACY; GLUCOSE BLOOD LEVEL; GOTO KAKIZAKI RAT; HEART EJECTION FRACTION; HEART FAILURE; HEART FUNCTION; HEART INFARCTION; HEART INFARCTION SIZE; HEART MUSCLE FIBROSIS; HEART VENTRICLE HYPERTROPHY; HEART VENTRICLE OVERLOAD; HYPERVOLEMIA; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; RAT; SYSTOLIC BLOOD PRESSURE; TREATMENT DURATION;

ACETAMIDES; ANIMALS; BIOLOGICAL MARKERS; CARDIAC VOLUME; CELL AGING; DIABETES MELLITUS, TYPE 2; FIBROSIS; HEART FAILURE; INFLAMMATION; MITOCHONDRIA, HEART; MYOCARDIAL INFARCTION; MYOCYTES, CARDIAC; PYRIDAZINES; RANDOM ALLOCATION; RATS; TETRAZOLES; TIME FACTORS; VALINE; VASODILATOR AGENTS; VENTRICULAR PRESSURE;

EID: 77950919230     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.00680.x     Document Type: Article

References (43)

1. Antila S, Sundberg S, Lehtonen LA (2007). Clinical pharmacology of levosimendan. Clin Pharmacokinet 46 : 535 552.
2. Baker DJ, Perez-Terzic C, Jin F, Pitel K, Niederlander NJ, Jeganathan K et al. (2008). Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nat Cell Biol 10 : 825 836.
3. 2 consumption in dogs. Am J Physiol Heart Circ Physiol 294 : H238 H248.
4. Bastide K, Guilly MN, Bernaudin JF, Joubert C, Lectard B, Levalois C et al. (2008). Molecular analysis of the Ink4a/Rb1-Arf/Tp53 pathways in radon-induced rat lung tumors. Lung Cancer 63 : 348 353.
5. Bowman P, Haikala H, Paul RJ (1999). Levosimendan, a calcium sensitizer in cardiac muscle, induces relaxation in coronary smooth muscle through calcium desensitization. J Pharmacol Exp Ther 288 : 316 325.
6. Cheng ZJ, Vaskonen T, Tikkanen I, Nurminen K, Ruskoaho H, Vapaatalo H et al. (2001). Endothelial dysfunction and salt-sensitive hypertension in spontaneously diabetic Goto-Kakizaki rats. Hypertension 37 : 433 439.
7. 2+ sensitizers. Circ J 72 : 1915 1925.
8. Erdei N, Papp Z, Pollesello P, Edes I, Bagi Z (2006). The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(ca) channels in rat isolated arterioles. Br J Pharmacol 148 : 696 702.
9. Galli J, Fakhrai-Rad H, Kamel A, Marcus C, Norgren S, Luthman H (1999). Pathophysiological and genetic characterization of the major diabetes locus in GK rats. Diabetes 48 : 2463 2470.
10. Garnier A, Fortin D, Delomenie C, Momken I, Veksler V, Ventura-Clapier R (2003). Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol 551 : 491 501.
11. Gaubatz S, Lindeman GJ, Ishida S, Jakoi L, Nevins JR, Livingston DM et al. (2000). E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control. Mol Cell 6 : 729 735.
12. Haikala H, Nissinen E, Etemadzadeh E, Levijoki J, Linden IB (1995). Troponin C-mediated calcium sensitization induced by levosimendan does not impair relaxation. J Cardiovasc Pharmacol 25 : 794 801.
13. Heyen JR, Blasi ER, Nikula K, Rocha R, Daust HA, Frierdich G et al. (2002). Structural, functional, and molecular characterization of the SHHF model of heart failure. Am J Physiol Heart Circ Physiol 283 : H1775 H1784.
14. Innes CA, Wagstaff AJ (2003). Levosimendan: a review of its use in the management of acute decompensated heart failure. Drugs 63 : 2651 2671.
15. Kivikko M, Lehtonen L, Colucci WS (2003). Sustained hemodynamic effects of intravenous levosimendan. Circulation 107 : 81 86.
16. Kopustinskiene DM, Pollesello P, Saris NE (2004). Potassium-specific effects of levosimendan on heart mitochondria. Biochem Pharmacol 68 : 807 812.
17. Levijoki J, Pollesello P, Kaheinen P, Haikala H (2001). Improved survival with simendan after experimental myocardial infarction in rats. Eur J Pharmacol 419 : 243 248.
18. Liu D, Jia H, Holmes DI, Stannard A, Zachary I (2003). Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDR-mediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1. Arterioscler Thromb Vasc Biol 23 : 2002 2007.
19. Louhelainen M, Vahtola E, Kaheinen P, Leskinen H, Merasto S, Kyto V et al. (2007). Effects of levosimendan on cardiac remodeling and cardiomyocyte apoptosis in hypertensive Dahl/Rapp rats. Br J Pharmacol 150 : 851 861.
20. Louhelainen M, Vahtola E, Forsten H, Merasto S, Kyto V, Finckenberg P et al. (2009). Oral levosimendan prevents postinfarct heart failure and cardiac remodeling in diabetic Goto-Kakizaki rats. J Hypertens 27 : 2094 2107.
21. Martinez-Gonzalez J, Badimon L (2005). The NR4A subfamily of nuclear receptors: new early genes regulated by growth factors in vascular cells. Cardiovasc Res 65 : 609 618.
22. Melzer D (2008). Genetic polymorphisms and human aging: association studies deliver. Rejuvenation Res 11 : 523 526.
23. Nieminen MS, Cleland JG, Eha J, Belenkov Y, Kivikko M, Poder P et al. (2008). Oral levosimendan in patients with severe chronic heart failure - the PERSIST study. Eur J Heart Fail 10 : 1246 1254.
24. Nieminen MS, Pollesello P, Vajda G, Papp Z (2009). Effects of levosimendan on the energy balance: preclinical and clinical evidence. J Cardiovasc Pharmacol 53 : 302 310.
25. Ohtani N, Brennan P, Gaubatz S, Sanij E, Hertzog P, Wolvetang E et al. (2003). Epstein-barr virus LMP1 blocks p16INK4a-RB pathway by promoting nuclear export of E2F4/5. J Cell Biol 162 : 173 183.
26. Ozdem SS, Yalcin O, Meiselman HJ, Baskurt OK, Usta C (2006). The role of potassium channels in relaxant effect of levosimendan in rat small mesenteric arteries. Cardiovasc Drugs Ther 20 : 123 127. (Pubitemid 43876095)
27. Palojoki E, Saraste A, Eriksson A, Pulkki K, Kallajoki M, Voipio-Pulkki LM et al. (2001a). Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol 280 : H2726 H2731.
28. Palojoki E, Saraste A, Eriksson A, Pulkki K, Kallajoki M, Voipio-Pulkki LM et al. (2001b). Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol 280 : H2726 H2731.
29. Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA et al. (1979). Myocardial infarct size and ventricular function in rats. Circ Res 44 : 503 512.
30. Pols TW, Bonta PI, de Vries CJ (2007). NR4A nuclear orphan receptors: protective in vascular disease? Curr Opin Lipidol 18 : 515 520.
31. Rota M, LeCapitaine N, Hosoda T, Boni A, De Angelis A, Padin-Iruegas ME et al. (2006). Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circ Res 99 : 42 52.
32. Sandell EP, Hayha M, Antila S, Heikkinen P, Ottoila P, Lehtonen LA et al. (1995). Pharmacokinetics of levosimendan in healthy volunteers and patients with congestive heart failure. J Cardiovasc Pharmacol 26 (Suppl 1 S57 S62.
33. Sano M, Fukuda K (2008). Activation of mitochondrial biogenesis by hormesis. Circ Res 103 : 1191 1193.
34. Segreti JA, Marsh KC, Polakowski JS, Fryer RM (2008). Evoked changes in cardiovascular function in rats by infusion of levosimendan, OR-1896 [(R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide], OR-1855 [(R)-6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one], dobutamine, and milrinone: comparative effects on peripheral resistance, cardiac output, dP/dt, pulse rate, and blood pressure. J Pharmacol Exp Ther 325 : 331 340.
35. Sharpless NE, DePinho RA (2007). How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8 : 703 713.
36. Sorsa T, Heikkinen S, Abbott MB, Abusamhadneh E, Laakso T, Tilgmann C et al. (2001). Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem 276 : 9337 9343.
37. Szilagyi S, Pollesello P, Levijoki J, Kaheinen P, Haikala H, Edes I et al. (2004). The effects of levosimendan and OR-1896 on isolated hearts, myocyte-sized preparations and phosphodiesterase enzymes of the guinea pig. Eur J Pharmacol 486 : 67 74.
38. 2+ transients under acidotic condition in aequorin-loaded canine ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol 366 : 440 448.
39. Takahashi R, Talukder MA, Endoh M (2000). Inotropic effects of OR-1896, an active metabolite of levosimendan, on canine ventricular myocardium. Eur J Pharmacol 400 : 103 112.
40. du Toit EF, Genis A, Opie LH, Pollesello P, Lochner A (2008). A role for the RISK pathway and K(ATP) channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig heart. Br J Pharmacol 154 : 41 50.
41. Vahtola E, Louhelainen M, Merasto S, Martonen E, Penttinen S, Aahos I et al. (2008). Forkhead class O transcription factor 3a activation and sirtuin1 overexpression in the hypertrophied myocardium of the diabetic Goto-Kakizaki rat. J Hypertens 26 : 334 344.
42. Wellner M, Dechend R, Park JK, Shagdarsuren E, Al-Saadi N, Kirsch T et al. (2005). Cardiac gene expression profile in rats with terminal heart failure and cachexia. Physiol Genomics 20 : 256 267.
43. Westhoff JH, Hilgers KF, Steinbach MP, Hartner A, Klanke B, Amann K et al. (2008). Hypertension induces somatic cellular senescence in rats and humans by induction of cell cycle inhibitor p16INK4a. Hypertension 52 : 123 129.