The cGMP/PKG pathway as a common mediator of cardioprotection: Translatability and mechanism

British Journal of Pharmacology

Volumn 172, Issue 8, 2015, Pages 1996-2009

  Inserte, Javier ^a   Garcia Dorado, David ^a  

^a HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO 5 CYCLOPROPYL 2 [1 (2 FLUOROBENZYL) 1H PYRAZOLO[3,4 B]PYRIDIN 3 YL]PYRIMIDINE; AMYL NITRITE; ARGININE; ATACIGUAT; ATRIAL NATRIURETIC FACTOR; BAY 60 2770; BRAIN NATRIURETIC PEPTIDE; CINACIGUAT; CYCLIC GMP; CYCLIC GMP DEPENDENT PROTEIN KINASE; GLYCERYL TRINITRATE; GUANYLATE CYCLASE; GUANYLATE CYCLASE ACTIVATOR; ISOSORBIDE MONONITRATE; LIFICIGUAT; NITRIC ACID DERIVATIVE; NITRIC OXIDE; NITRIC OXIDE DONOR; NITRITE; NOC 9; RIOCIGUAT; SEPIAPTERIN; SILDENAFIL; SNAP; SODIUM NITRITE; SOLUBLE GUANYLATE CYCLASE; TETRAHYDROBIOPTERIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; URODILATIN; VARDENAFIL; CARDIOTONIC AGENT;

CONTINUOUS INFUSION; DRUG MECHANISM; HEART INFARCTION; HEART INFARCTION PREVENTION; HEART MUSCLE REPERFUSION; HEART PROTECTION; HUMAN; ISCHEMIC HEART DISEASE; ISCHEMIC POSTCONDITIONING; ISCHEMIC PRECONDITIONING; NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REMOTE ISCHEMIC CONDITIONING; REPERFUSION INJURY; REVIEW; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; ANIMAL; DRUG EFFECTS; METABOLISM; MYOCARDIAL REPERFUSION INJURY; SIGNAL TRANSDUCTION;

ANIMALS; CARDIOTONIC AGENTS; CYCLIC GMP; CYCLIC GMP-DEPENDENT PROTEIN KINASES; HUMANS; MYOCARDIAL REPERFUSION INJURY; SIGNAL TRANSDUCTION;

EID: 84925864990     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12959     Document Type: Review

References (145)

1. Abdallah Y, Gkatzoflia A, Pieper H, Zoga E, Walther S, Kasseckert S, et al. (2005). Mechanism of cGMP-mediated protection in a cellular model of myocardial reperfusion injury. Cardiovasc Res 66: 123-131.
2. 2+ storage. Cardiovasc Res 70: 346-353.
3. Abdallah Y, Kasseckert SA, Iraqi W, Said M, Shahzad T, Erdogan A, et al. (2011). Interplay between Ca2+ cycling and mitochondrial permeability transition pores promotes reperfusion-induced injury of cardiac myocytes. J Cell Mol Med 15: 2478-2485.
4. Agullo L, Garcia-Dorado D, Inserte J, Paniagua A, Pyrhonen P, Llevadot J, et al. (1999). L-arginine limits myocardial cell death secondary to hypoxia-reoxygenation by a cGMP-dependent mechanism. Am J Physiol 276: H1574-H1580.
5. Agullo L, Garcia-Dorado D, Escalona N, Ruiz-Meana M, Inserte J, Soler-Soler J, (2003). Effect of ischemia on soluble and particulate guanylyl cyclase-mediated cGMP synthesis in cardiomyocytes. Am J Physiol Heart Circ Physiol 284: H2170-H2176.
6. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013a). The Concise Guide to PHARMACOLOGY 2013/14: Enzymes. Br J Pharmacol 170: 1797-1867.
7. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013b). The Concise Guide to PHARMACOLOGY 2013/14: Transporters. Br J Pharmacol 170: 1706-1796.
8. Andreka G, Vertesaljai M, Szantho G, Font G, Piroth Z, Fontos G, et al. (2007). Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs. Heart 93: 749-752.
9. Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M, (2008). Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation 117: 2340-2350.
10. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA, (1990). Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87: 1620-1624.
11. Bender AT, Beavo JA, (2006). Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58: 488-520.
12. Bice JS, Burley DS, Baxter GF, (2013). Novel approaches and opportunities for cardioprotective signaling through 3,5-cyclic guanosine monophosphate manipulation. J Cardiovasc Pharmacol Ther 19: 269-282.
13. Bice JS, Keim Y, Stasch JP, Baxter GF, (2014). NO-independent stimulation or activation of soluble guanylyl cyclase during early reperfusion limits infarct size. Cardiovasc Res 101: 220-228.
14. Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, et al. (2010). Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375: 727-734.
15. Breivik L, Helgeland E, Aarnes EK, Mrdalj J, Jonassen AK, (2010). Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion. Basic Res Cardiol 106: 135-145.
16. Burley DS, Baxter GF, (2007). B-type natriuretic peptide at early reperfusion limits infarct size in the rat isolated heart. Basic Res Cardiol 102: 529-541.
17. Castro LR, Verde I, Cooper DM, Fischmeister R, (2006). Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes. Circulation 113: 2221-2228.
18. Castro LR, Schittl J, Fischmeister R, (2010). Feedback control through cGMP-dependent protein kinase contributes to differential regulation and compartmentation of cGMP in rat cardiac myocytes. Circ Res 107: 1232-1240.
19. Ceremuzynski L, Budaj A, Czepiel A, Burzykowski T, Achremczyk P, Smielak-Korombel W, et al. (1999). Low-dose glucose-insulin-potassium is ineffective in acute myocardial infarction: results of a randomized multicenter Pol-GIK trial. Cardiovasc Drugs Ther 13: 191-200.
20. Cerra MC, Pellegrino D, (2007). Cardiovascular cGMP-generating systems in physiological and pathological conditions. Curr Med Chem 14: 585-599.
21. Chen W, Druhan LJ, Chen CA, Hemann C, Chen YR, Berka V, et al. (2010). Peroxynitrite induces destruction of the tetrahydrobiopterin and heme in endothelial nitric oxide synthase: transition from reversible to irreversible enzyme inhibition. Biochemistry 49: 3129-3137.
22. Cohen MV, Yang XM, Downey JM, (2007). The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation 115: 1895-1903.
23. Cohen MV, Yang XM, Liu Y, Solenkova NV, Downey JM, (2010). Cardioprotective PKG-independent NO signaling at reperfusion. Am J Physiol Heart Circ Physiol 299: H2028-H2036.
24. Costa MA, Elesgaray R, Balaszczuk AM, Arranz C, (2006). Role of NPR-C natriuretic receptor in nitric oxide system activation induced by atrial natriuretic peptide. Regul Pept 135: 63-68.
25. Das A, Xi L, Kukreja RC, (2008). Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta. J Biol Chem 283: 29572-29585.
26. Depre C, Hue L, (1994). Cyclic GMP in the perfused rat heart. Effect of ischaemia, anoxia and nitric oxide synthase inhibitor. FEBS Lett 345: 241-245.
27. Derbyshire ER, Marletta MA, (2012). Structure and regulation of soluble guanylate cyclase. Annu Rev Biochem 81: 533-559.
28. Diaz R, Paolasso EA, Piegas LS, Tajer CD, Moreno MG, Corvalan R, et al. (1998). Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group. Circulation 98: 2227-2234.
29. Donato M, Buchholz B, Rodriguez M, Perez V, Inserte J, Garcia-Dorado D, et al. (2013). Role of the parasympathetic nervous system in cardioprotection by remote hindlimb ischaemic preconditioning. Exp Physiol 98: 425-434.
30. Downey JM, Davis AM, Cohen MV, (2007). Signaling pathways in ischemic preconditioning. Heart Fail Rev 12: 181-188.
31. D'Souza SP, Yellon DM, Martin C, Schulz R, Heusch G, Onody A, et al. (2003). B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP channel opening. Am J Physiol Heart Circ Physiol 284: H1592-H1600.
32. Dumitrescu C, Biondi R, Xia Y, Cardounel AJ, Druhan LJ, Ambrosio G, et al. (2007). Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endothelial function ameliorated by BH4. Proc Natl Acad Sci U S A 104: 15081-15086.
33. Duranski MR, Greer JJ, Dejam A, Jaganmohan S, Hogg N, Langston W, et al. (2005). Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest 115: 1232-1240.
34. Ebner B, Ebner A, Reetz A, Bohme S, Schauer A, Strasser RH, et al. (2013). Pharmacological postconditioning by bolus injection of phosphodiesterase-5 inhibitors vardenafil and sildenafil. Mol Cell Biochem 379: 43-49.
35. Elrod JW, Greer JJ, Lefer DJ, (2007). Sildenafil-mediated acute cardioprotection is independent of the NO/cGMP pathway. Am J Physiol Heart Circ Physiol 292: H342-H347.
36. Erickson JR, He BJ, Grumbach IM, Anderson ME, (2011). CaMKII in the cardiovascular system: sensing redox states. Physiol Rev 91: 889-915.
37. Fan Q, Yang XC, Liu Y, Wang LF, Liu SH, Ge YG, et al. (2011). Postconditioning attenuates myocardial injury by reducing nitro-oxidative stress in vivo in rats and in humans. Clin Sci (Lond) 120: 251-261.
38. Follmann M, Griebenow N, Hahn MG, Hartung I, Mais FJ, Mittendorf J, et al. (2013). The chemistry and biology of soluble guanylate cyclase stimulators and activators. Angew Chem Int Ed Engl 52: 9442-9462.
39. Francis SH, Blount MA, Corbin JD, (2011). Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol Rev 91: 651-690.
40. Freixa X, Bellera N, Ortiz-Perez JT, Jimenez M, Pare C, Bosch X, et al. (2012). Ischaemic postconditioning revisited: lack of effects on infarct size following primary percutaneous coronary intervention. Eur Heart J 33: 103-112.
41. Fujita M, Asanuma H, Hirata A, Wakeno M, Takahama H, Sasaki H, et al. (2007). Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning. Am J Physiol Heart Circ Physiol 292: H2004-H2008.
42. Garcia-Dorado D, Ruiz-Meana M, Inserte J, Rodriguez-Sinovas A, Piper HM, (2012). Calcium-mediated cell death during myocardial reperfusion. Cardiovasc Res 94: 168-180.
43. Garcia-Dorado D, Rodriguez-Sinovas A, Ruiz-Meana M, Inserte J, (2014a). Protection against myocardial ischemia-reperfusion injury in clinical practice. Rev Esp Cardiol 67: 394-404.
44. Garcia-Dorado D, García-del-Blanco B, Otaegui I, Rodríguez-Palomares J, Pineda V, Gimeno F, et al. (2014b). Intracoronary injection of adenosine before reperfusion in patients with ST-segment elevation myocardial infarction: a randomized controlled clinical trial. Int J Cardiol http://dx.doi.org/10.1016/j.ijcard.2014.09.203 34: 669.
45. Geisbuhler TP, Schwager TL, (1996). Effect of anoxia on cyclic nucleotides and inositol phosphate turnover in cardiac myocytes. J Mol Cell Cardiol 28: 1857-1866.
46. Gomez L, Paillard M, Thibault H, Derumeaux G, Ovize M, (2008). Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion. Circulation 117: 2761-2768.
47. Gorbe A, Giricz Z, Szunyog A, Csont T, Burley DS, Baxter GF, et al. (2010). Role of cGMP-PKG signaling in the protection of neonatal rat cardiac myocytes subjected to simulated ischemia/reoxygenation. Basic Res Cardiol 105: 643-650.
48. Hahn JY, Song YB, Kim EK, Yu CW, Bae JW, Chung WY, et al. (2013). Ischemic postconditioning during primary percutaneous coronary intervention: the effects of postconditioning on myocardial reperfusion in patients with ST-segment elevation myocardial infarction (POST) randomized trial. Circulation 128: 1889-1896.
49. Halkos ME, Kerendi F, Corvera JS, Wang NP, Kin H, Payne CS, et al. (2004). Myocardial protection with postconditioning is not enhanced by ischemic preconditioning. Ann Thorac Surg 78: 961-969.
50. Hausenloy DJ, Tsang A, Yellon DM, (2005). The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 15: 69-75.
51. Hausenloy DJ, Iliodromitis EK, Andreadou I, Papalois A, Gritsopoulos G, Anastasiou-Nana M, et al. (2012). Investigating the signal transduction pathways underlying remote ischemic conditioning in the porcine heart. Cardiovasc Drugs Ther 26: 87-93.
52. Hausenloy DJ, Erik Botker H, Condorelli G, Ferdinandy P, Garcia-Dorado D, Heusch G, et al. (2013). Translating cardioprotection for patient benefit: position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res 98: 7-27.
53. Heusch G, (2012). Reduction of infarct size by ischaemic post-conditioning in humans: fact or fiction? Eur Heart J 33: 13-15.
54. Hoshida S, Yamashita N, Kawahara K, Kuzuya T, Hori M, (1999). Amelioration by quinapril of myocardial infarction induced by coronary occlusion/reperfusion in a rabbit model of atherosclerosis: possible mechanisms. Circulation 99: 434-440.
55. Inserte J, Garcia-Dorado D, Agullo L, Paniagua A, Soler-Soler J, (2000). Urodilatin limits acute reperfusion injury in the isolated rat heart. Cardiovasc Res 45: 351-359.
56. +-ATPase activity during early reperfusion contributes to cell death after myocardial ischemia. Circ Res 97: 465-473.
57. Inserte J, Barba I, Hernando V, Abellan A, Ruiz-Meana M, Rodriguez-Sinovas A, et al. (2008). Effect of acidic reperfusion on prolongation of intracellular acidosis and myocardial salvage. Cardiovasc Res 77: 782-790.
58. Inserte J, Barba I, Hernando V, Garcia-Dorado D, (2009). Delayed recovery of intracellular acidosis during reperfusion prevents calpain activation and determines protection in postconditioned myocardium. Cardiovasc Res 81: 116-122.
59. Inserte J, Ruiz-Meana M, Rodriguez-Sinovas A, Barba I, Garcia-Dorado D, (2011a). Contribution of delayed intracellular pH recovery to ischemic postconditioning protection. Antioxid Redox Signal 14: 923-939.
60. Inserte J, Barba I, Poncelas-Nozal M, Hernando V, Agullo L, Ruiz-Meana M, et al. (2011b). cGMP/PKG pathway mediates myocardial postconditioning protection in rat hearts by delaying normalization of intracellular acidosis during reperfusion. J Mol Cell Cardiol 50: 903-909.
61. Inserte J, Hernando V, Vilardosa U, Abad E, Poncelas-Nozal M, Garcia-Dorado D, (2013). Activation of cGMP/protein kinase G pathway in postconditioned myocardium depends on reduced oxidative stress and preserved endothelial nitric oxide synthase coupling. J Am Heart Assoc 2: e005975.
62. 2+ normalization and contributes to protection. Cardiovasc Res 103: 542-553.
63. Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, et al. (2004). Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113: 1535-1549.
64. Kaplan SH, Yang H, Gilliam DE, Shen J, Lemasters JJ, Cascio WE, (1995). Hypercapnic acidosis and dimethyl amiloride reduce reperfusion induced cell death in ischaemic ventricular myocardium. Cardiovasc Res 29: 231-238.
65. Kerendi F, Kin H, Halkos ME, Jiang R, Zatta AJ, Zhao ZQ, et al. (2005). Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res Cardiol 100: 404-412.
66. Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, et al. (2002). Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106: 2881-2883.
67. Kin H, Zhao ZQ, Sun HY, Wang NP, Corvera JS, Halkos ME, et al. (2004). Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 62: 74-85.
68. Kitakaze M, Asakura M, Kim J, Shintani Y, Asanuma H, Hamasaki T, et al. (2007). Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet 370: 1483-1493.
69. Kloner RA, Forman MB, Gibbons RJ, Ross AM, Alexander RW, Stone GW, (2006). Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial. Eur Heart J 27: 2400-2405.
70. Kopecky SL, Aviles RJ, Bell MR, Lobl JK, Tipping D, Frommell G, et al. (2003). A randomized, double-blinded, placebo-controlled, dose-ranging study measuring the effect of an adenosine agonist on infarct size reduction in patients undergoing primary percutaneous transluminal coronary angioplasty: the ADMIRE (AmP579 Delivery for Myocardial Infarction REduction) study. Am Heart J 146: 146-152.
71. Korkmaz S, Radovits T, Barnucz E, Hirschberg K, Neugebauer P, Loganathan S, et al. (2009). Pharmacological activation of soluble guanylate cyclase protects the heart against ischemic injury. Circulation 120: 677-686.
72. Krieg T, Liu Y, Rutz T, Methner C, Yang XM, Dost T, et al. (2009). BAY 58-2667, a nitric oxide-independent guanylyl cyclase activator, pharmacologically post-conditions rabbit and rat hearts. Eur Heart J 30: 1607-1613.
73. Kukreja RC, Salloum F, Das A, Ockaili R, Yin C, Bremer YA, et al. (2005). Pharmacological preconditioning with sildenafil: basic mechanisms and clinical implications. Vascul Pharmacol 42: 219-232.
74. Kukreja RC, Salloum FN, Das A, Koka S, Ockaili RA, Xi L, (2011). Emerging new uses of phosphodiesterase-5 inhibitors in cardiovascular diseases. Exp Clin Cardiol 16: e30-e35.
75. Lies B, Groneberg D, Gambaryan S, Friebe A, (2013). Lack of effect of ODQ does not exclude cGMP signalling via NO-sensitive guanylyl cyclase. Br J Pharmacol 170: 317-327.
76. Lochner A, Genade S, Tromp E, Opie L, Moolman J, Thomas S, et al. (1998). Role of cyclic nucleotide phosphodiesterases in ischemic preconditioning. Mol Cell Biochem 186: 169-175.
77. Lonborg J, Vejlstrup N, Kelbaek H, Botker HE, Kim WY, Mathiasen AB, et al. (2012). Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J 33: 1491-1499.
78. Lucas KA, Pitari GM, Kazerounian S, Ruiz-Stewart I, Park J, Schulz S, et al. (2000). Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev 52: 375-414.
79. Lundberg JO, Weitzberg E, Gladwin MT, (2008). The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7: 156-167.
80. Madhani M, Hall AR, Cuello F, Charles RL, Burgoyne JR, Fuller W, et al. (2010). Phospholemman Ser69 phosphorylation contributes to sildenafil-induced cardioprotection against reperfusion injury. Am J Physiol Heart Circ Physiol 299: H827-H836.
81. Mahaffey KW, Puma JA, Barbagelata NA, DiCarli MF, Leesar MA, Browne KF, et al. (1999). Adenosine as an adjunct to thrombolytic therapy for acute myocardial infarction: results of a multicenter, randomized, placebo-controlled trial: the Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial. J Am Coll Cardiol 34: 1711-1720.
82. Massion PB, Balligand JL, (2003). Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice. J Physiol 546: 63-75.
83. Mehta SR, Yusuf S, Diaz R, Zhu J, Pais P, Xavier D, et al. (2005). Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial. JAMA 293: 437-446.
84. Methner C, Lukowski R, Grube K, Loga F, Smith RA, Murphy MP, et al. (2013). Protection through postconditioning or a mitochondria-targeted S-nitrosothiol is unaffected by cardiomyocyte-selective ablation of protein kinase G. Basic Res Cardiol 108: 337.
85. Meurer S, Pioch S, Pabst T, Opitz N, Schmidt PM, Beckhaus T, et al. (2009). Nitric oxide-independent vasodilator rescues heme-oxidized soluble guanylate cyclase from proteasomal degradation. Circ Res 105: 33-41.
86. Moens AL, Kietadisorn R, Lin JY, Kass D, (2011). Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin. J Mol Cell Cardiol 51: 559-563.
87. Munzel T, Feil R, Mulsch A, Lohmann SM, Hofmann F, Walter U, (2003). Physiology and pathophysiology of vascular signaling controlled by guanosine 3,5-cyclic monophosphate-dependent protein kinase. Circulation 108: 2172-2183.
88. Murry CE, Jennings RB, Reimer KA, (1986). Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74: 1124-1136.
89. Nesher R, Robinson WF, Gibb L, Bishop SP, Kruger FA, (1977). Cyclic nucleotide levels in the perfused rat heart subjected to hypoxia. Experientia 33: 215-217.
90. Nishino Y, Webb IG, Davidson SM, Ahmed AI, Clark JE, Jacquet S, et al. (2008). Glycogen synthase kinase-3 inactivation is not required for ischemic preconditioning or postconditioning in the mouse. Circ Res 103: 307-314.
91. Ohashi T, Yamamoto F, Yamamoto H, Ichikawa H, Shibata T, Kawashima Y, (1996). Transient reperfusion with acidic solution affects postischemic functional recovery: studies in the isolated working rat heart. J Thorac Cardiovasc Surg 111: 613-620.
92. Ovize M, Baxter G, Di Lisa F, Ferdinandy P, Garcia-Dorado D, Hausenloy DJ, et al. (2010). Postconditioning and protection from reperfusion injury: where do we stand? Cardiovasc Res 87: 406-423.
93. Padilla F, Garcia-Dorado D, Agullo L, Inserte J, Paniagua A, Mirabet S, et al. (2000). L-Arginine administration prevents reperfusion-induced cardiomyocyte hypercontracture and reduces infarct size in the pig. Cardiovasc Res 46: 412-420.
94. Padilla F, Garcia-Dorado D, Agullo L, Barrabes JA, Inserte J, Escalona N, et al. (2001). Intravenous administration of the natriuretic peptide urodilatin at low doses during coronary reperfusion limits infarct size in anesthetized pigs. Cardiovasc Res 51: 592-600.
95. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP, et al.; NC-IUPHAR (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledge base of drug targets and their ligands. Nucl. Acids Res 42 (Database Issue): D1098-1106.
96. Penna C, Rastaldo R, Mancardi D, Raimondo S, Cappello S, Gattullo D, et al. (2006). Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K + channel and protein kinase C activation. Basic Res Cardiol 101: 180-189.
97. Penna C, Perrelli MG, Tullio F, Moro F, Parisella ML, Merlino A, et al. (2011). Post-ischemic early acidosis in cardiac postconditioning modifies the activity of antioxidant enzymes, reduces nitration, and favors protein S-nitrosylation. Pflugers Arch 462: 219-233.
98. Penna C, Perrelli MG, Pagliaro P, (2013). Mitochondrial pathways, permeability transition pore, and redox signaling in cardioprotection: therapeutic implications. Antioxid Redox Signal 18: 556-599.
99. Philipp S, Yang XM, Cui L, Davis AM, Downey JM, Cohen MV, (2006). Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade. Cardiovasc Res 70: 308-314.
100. Piper HM, Garcia-Dorado D, Ovize M, (1998). A fresh look at reperfusion injury. Cardiovasc Res 38: 291-300.
101. Piper HM, Kasseckert S, Abdallah Y, (2006). The sarcoplasmic reticulum as the primary target of reperfusion protection. Cardiovasc Res 70: 170-173.
102. Preckel B, Schlack W, Obal D, Barthel H, Ebel D, Grunert S, et al. (1998). Effect of acidotic blood reperfusion on reperfusion injury after coronary artery occlusion in the dog heart. J Cardiovasc Pharmacol 31: 179-186.
103. Rao YJ, Xi L, (2009). Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts. Acta Pharmacol Sin 30: 1-24.
104. Reffelmann T, Kloner RA, (2003). Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation. Cardiovasc Res 59: 441-449.
105. Ren B, Shen Y, Shao H, Qian J, Wu H, Jing H, (2007). Brain natriuretic peptide limits myocardial infarct size dependent of nitric oxide synthase in rats. Clin Chim Acta 377: 83-87.
106. Ruiz-Meana M, Abellan A, Miro-Casas E, Garcia-Dorado D, (2007). Opening of mitochondrial permeability transition pore induces hypercontracture in Ca2+ overloaded cardiac myocytes. Basic Res Cardiol 102: 542-552.
107. Salloum FN, Takenoshita Y, Ockaili RA, Daoud VP, Chou E, Yoshida K, et al. (2007). Sildenafil and vardenafil but not nitroglycerin limit myocardial infarction through opening of mitochondrial K(ATP) channels when administered at reperfusion following ischemia in rabbits. J Mol Cell Cardiol 42: 453-458.
108. Salloum FN, Das A, Samidurai A, Hoke NN, Chau VQ, Ockaili RA, et al. (2012). Cinaciguat, a novel activator of soluble guanylate cyclase, protects against ischemia/reperfusion injury: role of hydrogen sulfide. Am J Physiol Heart Circ Physiol 302: H1347-H1354.
109. Schmidt MR, Smerup M, Konstantinov IE, Shimizu M, Li J, Cheung M, et al. (2007). Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am J Physiol Heart Circ Physiol 292: H1883-H1890.
110. Schrammel A, Behrends S, Schmidt K, Koesling D, Mayer B, (1996). Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase. Mol Pharmacol 50: 1-5.
111. Selker HP, Udelson JE, Massaro JM, Ruthazer R, D'Agostino RB, Griffith JL, et al. (2014). One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial). Am J Cardiol 113: 1599-1605.
112. Shiva S, Sack MN, Greer JJ, Duranski M, Ringwood LA, Burwell L, et al. (2007). Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med 204: 2089-2102.
113. Siddiqi N, Neil C, Bruce M, MacLennan G, Cotton S, Papadopoulou S, et al. (2014). Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI). Eur Heart J 35: 1255-1262.
114. Siegmund B, Schlack W, Ladilov YV, Balser C, Piper HM, (1997). Halothane protects cardiomyocytes against reoxygenation-induced hypercontracture. Circulation 96: 4372-4379.
115. Skyschally A, van Caster P, Iliodromitis EK, Schulz R, Kremastinos DT, Heusch G, (2009a). Ischemic postconditioning: experimental models and protocol algorithms. Basic Res Cardiol 104: 469-483.
116. Skyschally A, van Caster P, Boengler K, Gres P, Musiolik J, Schilawa D, et al. (2009b). Ischemic postconditioning in pigs: no causal role for RISK activation. Circ Res 104: 15-18.
117. Sorensson P, Saleh N, Bouvier F, Bohm F, Settergren M, Caidahl K, et al. (2010). Effect of postconditioning on infarct size in patients with ST elevation myocardial infarction. Heart 96: 1710-1715.
118. Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, L'Huillier I, et al. (2005). Postconditioning the human heart. Circulation 112: 2143-2148.
119. Stangherlin A, Gesellchen F, Zoccarato A, Terrin A, Fields LA, Berrera M, et al. (2011). cGMP signals modulate cAMP levels in a compartment-specific manner to regulate catecholamine-dependent signaling in cardiac myocytes. Circ Res 108: 929-939.
120. Stasch JP, Schmidt PM, Nedvetsky PI, Nedvetskaya TY, Arun Kumar HS, Meurer S, et al. (2006). Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest 116: 2552-2561.
121. Szabo C, (1996). The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock 6: 79-88.
122. Tarantini G, Favaretto E, Marra MP, Frigo AC, Napodano M, Cacciavillani L, et al. (2012). Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial. Int J Cardiol 162: 33-38.
123. Thibault H, Piot C, Staat P, Bontemps L, Sportouch C, Rioufol G, et al. (2008). Long-term benefit of postconditioning. Circulation 117: 1037-1044.
124. Tiefenbacher CP, Chilian WM, Mitchell M, DeFily DV, (1996). Restoration of endothelium-dependent vasodilation after reperfusion injury by tetrahydrobiopterin. Circulation 94: 1423-1429.
125. Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, et al. (2009). Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 53: 501-510.
126. Tong G, Aponte AM, Kohr MJ, Steenbergen C, Murphy E, Sun J, (2014). Postconditioning leads to an increase in protein S-nitrosylation. Am J Physiol Heart Circ Physiol 306: H825-H832.
127. Tsai EJ, Kass DA, (2009). Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol Ther 122: 216-238.
128. Vasquez-Vivar J, Martasek P, Whitsett J, Joseph J, Kalyanaraman B, (2002). The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study. Biochem J 362: 733-739.
129. Verma S, Maitland A, Weisel RD, Fedak PW, Pomroy NC, Li SH, et al. (2002). Novel cardioprotective effects of tetrahydrobiopterin after anoxia and reoxygenation: identifying cellular targets for pharmacologic manipulation. J Thorac Cardiovasc Surg 123: 1074-1083.
130. Vila-Petroff M, Mundina-Weilenmann C, Lezcano N, Snabaitis AK, Huergo MA, Valverde CA, et al. (2009). Ca(2+)/calmodulin-dependent protein kinase II contributes to intracellular pH recovery from acidosis via Na(+)/H(+) exchanger activation. J Mol Cell Cardiol 49: 106-112.
131. Webb A, Bond R, McLean P, Uppal R, Benjamin N, Ahluwalia A, (2004). Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci U S A 101: 13683-13688.
132. Woo JS, Kim W, Ha SJ, Kim JB, Kim SJ, Kim WS, et al. (2013). Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study. Arterioscler Thromb Vasc Biol 33: 2252-2260.
133. Worner R, Lukowski R, Hofmann F, Wegener JW, (2007). cGMP signals mainly through cAMP kinase in permeabilized murine aorta. Am J Physiol Heart Circ Physiol 292: H237-H244.
134. Xia Y, Tsai AL, Berka V, Zweier JL, (1998). Superoxide generation from endothelial nitric-oxide synthase. A Ca2+/calmodulin-dependent and tetrahydrobiopterin regulatory process. J Biol Chem 273: 25804-25808.
135. Xin P, Zhu W, Li J, Ma S, Wang L, Liu M, et al. (2010). Combined local ischemic postconditioning and remote perconditioning recapitulate cardioprotective effects of local ischemic preconditioning. Am J Physiol Heart Circ Physiol 298: H1819-H1831.
136. Yamaguchi F, Nasa Y, Yabe K, Ohba S, Hashizume Y, Ohaku H, et al. (1997). Activation of cardiac muscarinic receptor and ischemic preconditioning effects in in situ rat heart. Heart Vessels 12: 74-83.
137. Yamashiro S, Noguchi K, Matsuzaki T, Miyagi K, Nakasone J, Sakanashi M, et al. (2002). Beneficial effect of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts. J Thorac Cardiovasc Surg 124: 775-784.
138. Yang X, Cohen MV, Downey JM, (2010). Mechanism of cardioprotection by early ischemic preconditioning. Cardiovasc Drugs Ther 24: 225-234.
139. Yang XM, Proctor JB, Cui L, Krieg T, Downey JM, Cohen MV, (2004). Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways. J Am Coll Cardiol 44: 1103-1110.
140. Yellon DM, Hausenloy DJ, (2007). Myocardial reperfusion injury. N Engl J Med 357: 1121-1135.
141. Yuan SY, (2002). Protein kinase signaling in the modulation of microvascular permeability. Vascul Pharmacol 39: 213-223.
142. Zaccolo M, Movsesian MA, (2007). cAMP and cGMP signaling cross-talk: role of phosphodiesterases and implications for cardiac pathophysiology. Circ Res 100: 1569-1578.
143. Zhang M, Kass DA, (2011). Phosphodiesterases and cardiac cGMP: evolving roles and controversies. Trends Pharmacol Sci 32: 360-365.
144. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, et al. (2003). Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285: H579-H588.
145. Zhou Z, Pyriochou A, Kotanidou A, Dalkas G, van Eickels M, Spyroulias G, et al. (2008). Soluble guanylyl cyclase activation by HMR-1766 (ataciguat) in cells exposed to oxidative stress. Am J Physiol Heart Circ Physiol 295: H1763-H1771.