Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine coronary endothelial cells: Role for mitochondrial K ATP channel

British Journal of Pharmacology

Volumn 156, Issue 2, 2009, Pages 250-261

  Grossini, E ^a   Molinari, C ^a   Caimmi, P P ^a   Uberti, F ^a   Vacca, G ^a  

^a UNIVERSITY OF CHIETI   (Italy)

Author keywords

Akt involvement; Coronary endothelial cells; ERK; K ATP channel; Levosimendan; Nitric oxide production; P38

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 CYANO 1 (1,1 DIMETHYLPROPYL) 3 (3 PYRIDYL)GUANIDINE; 2' ,5' DIDEOXYADENOSINE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 5 HYDROXYDECANOIC ACID; ADENOSINE TRIPHOSPHATE; ADENYLATE CYCLASE INHIBITOR; CROMAKALIM; DIAZOXIDE; DIMETHYL SULFOXIDE; DRUG VEHICLE; FORSKOLIN; GLIBENCLAMIDE; LEVOSIMENDAN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; N(G) NITROARGININE METHYL ESTER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE INHIBITOR; POTASSIUM CHANNEL; PROTEIN KINASE B; UNCLASSIFIED DRUG; ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; ADENYLATE CYCLASE; CYCLIC AMP; ENDOTHELIAL NITRIC OXIDE SYNTHASE; HYDRAZONE DERIVATIVE; MITOCHONDRIAL K(ATP) CHANNEL; PHOSPHATIDYLINOSITOL 3 KINASE; PYRIDAZINE DERIVATIVE; SIMENDAN; VASODILATOR AGENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CORONARY ARTERY BLOOD FLOW; DRUG MECHANISM; ENDOTHELIUM CELL; INTRACELLULAR TRANSPORT; MEMBRANE TRANSPORT; MITOCHONDRIAL MEMBRANE; NONHUMAN; POTASSIUM TRANSPORT; PRIORITY JOURNAL; SWINE; VASODILATATION; ANIMAL; BIOSYNTHESIS; CELL CULTURE; CHANNEL GATING; CORONARY BLOOD VESSEL; CYTOLOGY; DOSE RESPONSE; DRUG ANTAGONISM; DRUG EFFECT; DRUG POTENTIATION; ENZYME ACTIVATION; IN VITRO STUDY; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADENYLATE CYCLASE; ANIMALS; CELLS, CULTURED; CORONARY VESSELS; CYCLIC AMP; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOTHELIAL CELLS; ENZYME ACTIVATION; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HYDRAZONES; ION CHANNEL GATING; KATP CHANNELS; NG-NITROARGININE METHYL ESTER; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PHOSPHORYLATION; POTASSIUM CHANNELS; PROTO-ONCOGENE PROTEINS C-AKT; PYRIDAZINES; SWINE; VASODILATOR AGENTS;

EID: 67650242870     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2008.00024.x     Document Type: Article

References (59)

1. Akar F, Manavbasi Y, Parlar AI, Ulus AT, Katircioglu SF (2007). The gender differences in the relaxation to levosimendan of human internal mammary artery. Cardiovasc Drugs Ther 21 : 331 338.
2. Alexander SPH, Mathie A, Peters JA (2008). Guide to Receptors and Channels (GRAC), 3rd edition (2008 revision). Br J Pharmacol 153 (Suppl. 2 S1 S209.
3. Andrukhiv A, Costa AD, West IC, Garlid KD (2006). Opening mitoKATP increases superoxide generation from complex I of the electron transport chain. Am J Physiol Heart Circ Physiol 291 : H2067 H2074.
4. Baczkó I, Jones L, McGuigan CF, Manning Fox JE, Gandhi M, Giles WR et al. (2005). Plasma membrane KATP channel-mediated cardioprotection involves posthypoxic reductions in calcium overload and contractile dysfunction: mechanistic insights into cardioplegia. FASEB J 19 : 980 982.
5. Bogle RG, Baydoun AR, Pearson JD, Mann GE (1996). Regulation of L-arginine transport and nitric oxide release in superfused porcine aortic endothelial cells. J Physiol 490 : 229 241.
6. Bokník P, Neumann J, Kaspareit G, Schmitz W, Scholz H, Vahlensieck U et al. (1997). Mechanisms of the contractile effects of levosimendan in the mammalian heart. J Pharmacol Exp Ther 280 : 277 283.
7. Boo YC, Hwang J, Sykes M (2002). Shear stress stimulates phosphorylation of eNOS at Ser (635) by a protein kinase A-dependent mechanism. Am J Physiol Heart Circ Physiol 283 : H1819 H1828.
8. 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.
9. Bryan PT, Marshall JM (1999). Cellular mechanisms by which adenosine induces vasodilatation in rat skeletal muscle: significance for systemic hypoxia. J Physiol 514 : 163 175.
10. Busse R, Lückhoff A, Mülsch A (1991). Cellular mechanisms controlling EDRF/NO formation in endothelial cells. Basic Res Cardiol 86 : 7 16.
11. Cuong DV, Kim N, Youm JB, Joo H, Warda M, Lee JW et al. (2002). Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416 : 337 339.
12. Das B, Sarkar C (2007). Pharmacological preconditioning by levosimendan is mediated by inducible nitric oxide synthase and mitochondrial KATP channel activation in the in vivo anesthetized rabbit heart model. Vascul Pharmacol 47 : 248 256.
13. 2+ sensitizers rescue patients from chronic congestive heart failure? Br J Pharmacol 150 : 826 828.
14. 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.
15. Fulton D, Gratton JP, Sessa WC (2001). Post-translational control of endothelial nitric oxide synthase: why isn't calcium/calmodulin enough? J Pharmacol Exp Ther 299 : 818 824.
16. Gross GJ, Fryer MR (1999). Sarcolemmal versus mitochondrial ATP-sensitive K+ channels and myocardial preconditioning. Circ Res 84 : 973 979.
17. Grossini E, Caimmi PP, Molinari C, Teodori G, Vacca G (2005). Hemodynamic effect of intracoronary administration of levosimendan in the anesthetized pig. J Cardiovasc Pharmacol 46 : 333 342.
18. Grossini E, Molinari C, Mary DA, Uberti F, Caimmi PP, Surico N et al. (2008). Intracoronary genistein acutely increases coronary blood flow in anesthetized pigs through β adrenergic mediated nitric oxide release and estrogenic receptors. Endocrinology 149 : 2678 2687.
19. Gruhn N, Nielsen-Kudsk JE, Theilgaard S, Bang L, Olesen SP, Aldershvile J (1998). Coronary vasorelaxant effect of levosimendan, a new inodilator with calcium-sensitizing properties. J Cardiovasc Pharmacol 31 : 741 749.
20. Haikala H, Linden IB (1995). Mechanisms of action of calcium sensitizing drugs. J Cardiovasc Pharmacol 26 : S10 S19.
21. Han J, Kim N, Joo H, Kim E, Earm YE (2002). ATP-sensitive K+ channel activation by nitric oxide and protein kinase G in rabbit ventricular myocytes. Am J Physiol Heart Circ Physiol 283 : H1545 H1554.
22. Hashimoto A, Miyakoda G, Hirose Y, Mori T (2006). Activation of endothelial nitric oxide synthase by cilostazol via a cAMP/protein kinase A- and phosphatidylinositol 3-kinase/Akt-dependent mechanism. Atherosclerosis 189 : 350 357.
23. Herrera GM, Resta TC, Candelaria JJ, Walker BR (1998). Maintained vasodilatory response to cromakalim after inhibition of nitric oxide synthesis. J Cardiovasc Pharmacol 31 : 921 929.
24. Höhn J, Pataricza J, Petri A, Tóth GK, Balogh A, Varró A et al. (2004). Levosimendan interacts with potassium channel blockers in human saphenous veins. Basic Clin Pharmacol Toxicol 94 : 271 273.
25. Ito C, Kusano E, Akimoto T (2002). Cilostazol enhances IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle via PKA-dependent pathway. Cell Signal 14 : 625 632.
26. Jackson WF (2005). Potassium channels in the peripheral microcirculation. Microcirculation 12 : 113 127.
27. Janigro D, West GA, Gordon EL, Winn HR (1993). ATP-sensitive K+ channels in rat aorta and brain microvascular endothelial cells. Am J Physiol 265 : C812 C821.
28. Janigro D, Nguyen TS, Meno J, West GA, Winn HR (1997). Endothelium-dependent regulation of cerebrovascular tone by extracellular and intracellular ATP. Am J Physiol 273 : H878 H885.
29. John TA, Ibe BO, Raj JU (2008). Regulation of endothelial nitric oxide synthase: involvement of protein kinase G 1beta, serine 116 phosphorylation and lipid structures. Clin Exp Pharmacol Physiol 35 : 148 158.
30. Kaheinen P, Pollesello P, Levijoki J, Haikala H (2001). Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels. J Cardiovasc Pharmacol 37 : 367 374.
31. Kersten JR, Montgomery MW, Pagel PS, Warltier DC (2000). Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of K(ATP) channels. Anesth Analg 90 : 5 11.
32. Kimura C, Oike M, Ohnaka K, Nose Y, Ito Y (2004). Constitutive nitric oxide production in bovine aortic and brain microvascular endothelial cells: a comparative study. J Physiol 554 : 721 730.
33. Kopustinskiene DM, Pollesello P, Saris NE (2001). Levosimendan is a mitochondrial K(ATP) channel opener. Eur J Pharmacol 428 : 311 314.
34. Kopustinskiene DM, Pollesello P, Saris NE (2004). Potassium-specific effects of levosimendan on heart mitochondria. Biochem Pharmacol 68 : 807 812.
35. Koyama T, Kimura C, Park SJ, Oike M, Ito Y (2002). Functional implications of Ca2+ mobilizing properties for nitric oxide production in aortic endothelium. Life Sci 72 : 511 520.
36. Lorenz M, Wessler S, Follmann E, Michaelis W, Düsterhöft T, Baumann G et al. (2004). A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH- kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. J Biol Chem 279 : 6190 6195.
37. Luckhoff A, Busse R (1990). Calcium influx into endothelial cells and formation of endothelium-derived relaxing factor is controlled by the membrane potential. Pflugers Arch 416 : 305 311.
38. Luo SS, Sugimoto K, Fujii S, Takemasa T, Fu SB, Yamashita K (2007). Role of heat shock protein 70 in induction of stress fiber formation in rat arterial endothelial cells in response to stretch stress. Acta Histochem Cytochem 40 : 9 17.
39. Michaels AD, McKeown B, Kostal M, Vakharia KT, Jordan MV, Gerber IL et al. (2005). Effects of intravenous levosimendan on human coronary vasomotor regulation, left ventricular wall stress, and myocardial oxygen uptake. Circulation 111 : 1504 1509.
40. Molinari C, Grossini E, Mary DA, Uberti F, Ghigo E, Ribichini F et al. (2007). Prolactin induces regional vasoconstriction through the beta2-adrenergic and nitric oxide mechanisms. Endocrinology 148 : 4080 4090.
41. Nelson MT, Quayle JM (1995). Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 268 : C799 C822.
42. Nilius B, Droogmans G (2001). Ion channels and their functional role in vascular endothelium. Physiol Rev 81 : 1415 1459.
43. Oldenburg O, Qin Q, Sharma A, Cohen M, Downey J, Benoit J (2002). Acetylcholine leads to free radical production dependent on KATP channels, Gi proteins, phosphatidylinositol 3-kinase and tyrosine kinase. Cardiovasc Res 55 : 544 552.
44. Padmasekar M, Nandigama R, Wartenberg M, Schluter KD, Sauer H (2007). The acute phase protein alpha2-macroglobulin induces rat ventricular cardiomyocyte hypertrophy via ERK1,2 and PI3-kinase/Akt pathways. Cardiovasc Res 75 : 118 128.
45. Pasdois P, Beauvoit B, Tariosse L, Vinassa B, Bonoron-Adèle S, Santos PD (2006). MitoK(ATP)-dependent changes in mitochondrial volume and in complex II activity during ischemic and pharmacological preconditioning of Langendorff-perfused rat heart. J Bioenerg Biomembr 38 : 101 112.
46. Pasdois P, Quinlan CL, Rissa A, Tariosse L, Vinassa B, Costa AD et al. (2007). Ouabain protects rat hearts against ischemia-reperfusion injury via pathway involving src kinase, mitoKATP, and ROS. Am J Physiol Heart Circ Physiol 292 : H1470 H1478.
47. Pataricza J, Hõhn J, Petri A, Balogh A, Papp JG (2000). Comparison of the vasorelaxing effect of cromakalim and the new inodilator, levosimendan, in human isolated portal vein. J Pharm Pharmacol 52 : 213 217.
48. Polte T, Schröder H (1998). Cyclic AMP mediates endothelial protection by nitric oxide. Biochem Biophys Res Commun 20 : 460 465.
49. Sheng JZ, Braun AP (2007). Small- and intermediate-conductance Ca2+-activated K+ channels directly control agonist-evoked nitric oxide synthesis in human vascular endothelial cells. Am J Physiol Cell Physiol 293 : C458 C467.
50. Simoncíková P, Ravingerová T, Andelová E, Tribulová N, Barancík M (2007). Changes in rat myocardium associated with modulation of ischemic tolerance by diazoxide. Gen Physiol Biophys 26 : 75 85.
51. Sobrevia L, Cesare P, Yudilevich DL, Mann GE (1995). Diabetes-induced activation of system y+ and nitric oxide synthase in human endothelial cells: association with membrane hyperpolarization. J Physiol 489 : 183 192.
52. Stankevicius E, Lopez-Valverde V, Rivera L, Hughes AD, Mulvany MJ, Simonsen U (2006). Combination of Ca2+ -activated K+ channel blockers inhibits acetylcholine-evoked nitric oxide release in rat superior mesenteric artery. Br J Pharmacol 149 : 560 572.
53. 2+ sensitivity by levosimendan in normal and acidotic conditions in aequorin-loaded canine ventricular myocardium. Br J Pharmacol 145 : 1143 1152.
54. 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.
55. Wyatt WA, Steinert JR, Mann GE (2004). Modulaiton of the L-arginine/nitric oxide signalling pathway in vascular endothelial cells. Biochem Soc Symp 71 : 143 156.
56. Xu Z, Ji X, Boysen PG (2004). Exogenous nitric oxide generates ROS and induces cardioprotection: involvement of PKG, mitochondrial KATP channels, and ERK. Am J Physiol Heart Circ Physiol 286 : H1433 H1440.
57. Yildiz O (2007). Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci 104 : 1 5.
58. Yokoshiki H, Katsube Y, Sunagawa M, Sperelakis N (1997). Levosimendan, a novel Ca++ sensitizer, activates the glibenclamide sensitive K+ channel in rat arterial myocytes. Eur J Pharmacol 333 : 249 259. (Pubitemid 27387398)
59. Zoltán P, Kálmán C, Pollesello P, Haikala H, Édes I (2005). Pharmacological mechanisms contributing to the clinical efficacy of levosimendan. Cardiovasc Drug Rev 23 : 71 98.