Why does exercise “trigger” adaptive protective responses in the heart?

Dose-Response

Volumn 13, Issue 1, 2015, Pages 1-19

  Alleman, Rick J ^a   Stewart, Luke M ^a   Tsang, Alvin M ^a   Brown, David A ^a  

^a EAST CAROLINA UNIVERSITY   (United States)

Author keywords

Cardiac; Exercise; Heart; Mitochondria; Preconditioning

Indexed keywords

ADENOSINE; CYTOKINE; NITRIC OXIDE; OPIATE; PROTEIN KINASE; REACTIVE OXYGEN METABOLITE;

ADAPTATION; ARTICLE; EXERCISE; EXERCISE PRECONDITIONING; HEART ARRHYTHMIA; HEART INFARCTION; HEART PROTECTION; HUMAN; MORBIDITY; MORTALITY; NONHUMAN; PHENOTYPE; SIGNAL TRANSDUCTION;

EID: 84929340606     PISSN: None     EISSN: 15593258     Source Type: Journal    
DOI: 10.2203/dose-response.14-023.Alleman     Document Type: Article

References (109)

1. Akita Y, Otani H, Matsuhisa S, Kyoi S, Enoki C, Hattori R, Imamura H, Kamihata H, Kimura Y and Iwasaka T. 2007. Exercise-induced activation of cardiac sympathetic nerve triggers cardioprotection via redox-sensitive activation of eNOS and upregulation of iNOS. Am J Physiol Heart Circ Physiol 292:H2051-9
2. Babai L, Szigeti Z, Parratt JR and Vegh A. 2002. Delayed cardioprotective effects of exercise in dogs are aminoguanidine sensitive: possible involvement of nitric oxide. Clin Sci (Lond) 102:435-45
3. Baines CP, Goto M and Downey JM. 1997. Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium. J Mol Cell Cardiol 29:207-16
4. Barbosa VA, Luciano TF, Marques SO, Vitto MF, Souza DR, Silva LA, Santos JP, Moreira JC, Dal-Pizzol F, Lira FS, Pinho RA and De Souza CT. 2013. Acute exercise induce endothelial nitric oxide synthase phosphorylation via Akt and AMP-activated protein kinase in aorta of rats: Role of reactive oxygen species. Int J Cardiol 167:2983-8
5. Bhushan S, Kondo K, Predmore BL, Zlatopolsky M, King AL, Pearce C, Huang H, Tao YX, Condit ME and Lefer DJ. 2012. Selective beta2-adrenoreceptor stimulation attenuates myocardial cell death and preserves cardiac function after ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 32:1865-74
6. Bianchi P, Kunduzova O, Masini E, Cambon C, Bani D, Raimondi L, Seguelas MH, Nistri S, Colucci W, Leducq N and Parini A. 2005. Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte apoptosis by serotonin and postischemic myocardial injury. Circulation 112:3297-305
7. Blais C, Jr., Adam A, Massicotte D and Peronnet F. 1999. Increase in blood bradykinin concentration after eccentric weight-training exercise in men. J Appl Physiol (1985) 87:1197-201
8. Bloch W, Addicks K, Hescheler J and Fleischmann BK. 2001. Nitric oxide synthase expression and function in embryonic and adult cardiomyocytes. Microsc Res Tech 55:259-69
9. Bolli R. 1988. Oxygen-derived free radicals and postischemic myocardial dysfunction (“stunned myocardium”). J Am Coll Cardiol 12:239-49
10. Bolli R, Jeroudi MO, Patel BS, Aruoma OI, Halliwell B, Lai EK and McCay PB. 1989. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocardial “stunning” is a manifestation of reperfusion injury. Circ Res 65:607-22
11. Bowles DK, Farrar RP and Starnes JW. 1992. Exercise training improves cardiac function after ischemia in the isolated, working rat heart. Am J Physiol 263:H804-9
12. Brown DA, Chicco AJ, Jew KN, Johnson MS, Lynch JM, Watson PA and Moore RL. 2005a. Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat. J Physiol 569:913-24
13. Brown DA, Jew KN, Sparagna GC, Musch TI and Moore RL. 2003. Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart. J Appl Physiol (1985) 95:2510-8
14. Brown DA, Lynch JM, Armstrong CJ, Caruso NM, Ehlers LB, Johnson MS and Moore RL. 2005b. Susceptibility of the heart to ischaemia-reperfusion injury and exercise-induced cardioprotection are sex-dependent in the rat. J Physiol 564:619-30
15. Brown DA and Moore RL. 2007. Perspectives in innate and acquired cardioprotection: cardioprotection acquired through exercise. J Appl Physiol (1985) 103:1894-9
16. Brown JM, White CW, Terada LS, Grosso MA, Shanley PF, Mulvin DW, Banerjee A, Whitman GJ, Harken AH and Repine JE. 1990. Interleukin 1 pretreatment decreases ischemia/reperfusion injury. Proc Natl Acad Sci U S A 87:5026-30
17. Bryan NS, Calvert JW, Elrod JW, Gundewar S, Ji SY and Lefer DJ. 2007. Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury. Proc Natl Acad Sci U S A 104:19144-9
18. Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, Maloney RE, Bharti A, Rodriguez J and Feelisch M. 2005. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol 1:290-7
19. Calvert JW, Condit ME, Aragon JP, Nicholson CK, Moody BF, Hood RL, Sindler AL, Gundewar S, Seals DR, Barouch LA and Lefer DJ. 2011. Exercise protects against myocardial ischemia-reperfusion injury via stimulation of beta(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols. Circ Res 108:1448-58
20. Chandrasekera PC, McIntosh VJ, Cao FX and Lasley RD. 2010. Differential effects of adenosine A2a and A2b receptors on cardiac contractility. Am J Physiol Heart Circ Physiol 299:H2082-9
21. Chouchani ET, Methner C, Nadtochiy SM, Logan A, Pell VR, Ding S, James AM, Cocheme HM, Reinhold J, Lilley KS, Partridge L, Fearnley IM, Robinson AJ, Hartley RC, Smith RA, Krieg T, Brookes PS and Murphy MP. 2013. Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med 19:753-9
22. Coven DL, Hu X, Cong L, Bergeron R, Shulman GI, Hardie DG and Young LH. 2003. Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise. Am J Physiol Endocrinol Metab 285:E629-36
23. Dabkowski ER, Williamson CL and Hollander JM. 2008. Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/ reperfusion-associated cardiac dysfunction. Free Radic Biol Med 45:855-65
24. Debruille C, Luyckx M, Ballester L, Brunet C, Odou P, Dine T, Gressier B, Cazin M and Cazin JC. 1999. Serum opioid activity after physical exercise in rats. Physiol Res 48:129-33
25. Demirel HA, Powers SK, Zergeroglu MA, Shanely RA, Hamilton K, Coombes J and Naito H. 2001. Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. J Appl Physiol (1985) 91:2205-12
26. Dickson EW, Hogrefe CP, Ludwig PS, Ackermann LW, Stoll LL and Denning GM. 2008. Exercise enhances myocardial ischemic tolerance via an opioid receptor-dependent mechanism. Am J Physiol Heart Circ Physiol 294:H402-8
27. Domenech R, Macho P, Schwarze H and Sanchez G. 2002. Exercise induces early and late myocardial preconditioning in dogs. Cardiovasc Res 55:561-6
28. Domenech RJ, Macho P, Velez D, Sanchez G, Liu X and Dhalla N. 1998. Tachycardia preconditions infarct size in dogs: role of adenosine and protein kinase C. Circulation 97:786-94
29. Donges CE, Duffield R, Smith GC, Short MJ and Edge JA. 2014. Cytokine mRNA expression responses to resistance, aerobic, and concurrent exercise in sedentary middle-aged men. Appl Physiol Nutr Metab 39:130-7
30. Donoso P, Finkelstein JP, Montecinos L, Said M, Sanchez G, Vittone L and Bull R. 2014. Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium. J Mol Cell Cardiol 68:38-46
31. Eddy LJ, Goeddel DV and Wong GH. 1992. Tumor necrosis factor-alpha pretreatment is protective in a rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun 184:1056-9
32. Farah C, Kleindienst A, Bolea G, Meyer G, Gayrard S, Geny B, Obert P, Cazorla O, Tanguy S and Reboul C. 2013. Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites. Basic Res Cardiol 108:389
33. Frasier CR, Moore RL and Brown DA. 2011a. Exercise-induced cardiac preconditioning: how exercise protects your achy-breaky heart. J Appl Physiol 111:905-15
34. Frasier CR, Moukdar F, Patel HD, Sloan RC, Stewart LM, Alleman RJ, La Favor JD and Brown DA. 2013. Redox-dependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria. Cardiovasc Res 98:47-55
35. Frasier CR, Sloan RC, Bostian PA, Gonzon MD, Kurowicki J, Lopresto SJ, Anderson EJ and Brown DA. 2011b. Short-term exercise preserves myocardial glutathione and decreases arrhythmias after thiol oxidation and ischemia in isolated rat hearts. J Appl Physiol 111:1751-9
36. Frederich M and Balschi JA. 2002. The relationship between AMP-activated protein kinase activity and AMP concentration in the isolated perfused rat heart. J Biol Chem 277:1928-32
37. Fredholm BB, AP IJ, Jacobson KA, Linden J and Muller CE. 2011. International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors—an update. Pharmacol Rev 63:1-34
38. French JP, Hamilton KL, Quindry JC, Lee Y, Upchurch PA and Powers SK. 2008. Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain. FASEB J 22:2862-71
39. Fryer RM, Hsu AK, Eells JT, Nagase H and Gross GJ. 1999. Opioid-induced second window of cardioprotection: potential role of mitochondrial KATP channels. Circ Res 84:846-51
40. Galvao TF, Matos KC, Brum PC, Negrao CE, Luz PL and Chagas AC. 2011. Cardioprotection conferred by exercise training is blunted by blockade of the opioid system. Clinics (Sao Paulo) 66:151-7
41. Garlid AO, Jaburek M, Jacobs JP and Garlid KD. 2013. Mitochondrial reactive oxygen species: which ROS signals cardioprotection? Am J Physiol Heart Circ Physiol 305:H960-8
42. Gauthier C, Leblais V, Kobzik L, Trochu JN, Khandoudi N, Bril A, Balligand JL and Le Marec H. 1998. The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle. J Clin Invest 102:1377-84
43. Hamalainen H, Luurila OJ, Kallio V and Knuts LR. 1995. Reduction in sudden deaths and coronary mortality in myocardial infarction patients after rehabilitation. 15 year follow-up study. Eur Heart J 16:1839-44
44. Hamilton KL, Powers SK, Sugiura T, Kim S, Lennon S, Tumer N and Mehta JL. 2001. Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins. Am J Physiol Heart Circ Physiol 281:H1346-52
45. Hamilton KL, Quindry JC, French JP, Staib J, Hughes J, Mehta JL and Powers SK. 2004. MnSOD antisense treatment and exercise-induced protection against arrhythmias. Free Radic Biol Med 37:1360-8
46. Harzand A, Tamariz L and Hare JM. 2012. Uric acid, heart failure survival, and the impact of xanthine oxidase inhibition. Congest Heart Fail 18:179-82
47. Horwitz LD, Fennessey PV, Shikes RH and Kong Y. 1994. Marked reduction in myocardial infarct size due to prolonged infusion of an antioxidant during reperfusion. Circulation 89:1792-801
48. Hoshida S, Yamashita N, Otsu K and Hori M. 2002. Repeated physiologic stresses provide persistent cardioprotection against ischemia-reperfusion injury in rats. J Am Coll Cardiol 40:826-31
49. Husain K and Somani SM. 2005. Interaction of exercise and adenosine receptor agonist and antagonist on rat heart antioxidant defense system. Mol Cell Biochem 270:209-14
50. Jacobson KA, Balasubramanian R, Deflorian F and Gao ZG. 2012. G protein-coupled adenosine (P1) and P2Y receptors: ligand design and receptor interactions. Purinergic Signal 8:419-36
51. Jones DP. 2008. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol 295:C849-68
52. Kakarla P, Vadluri G, Reddy KS and Leeuwenburgh C. 2005. Vulnerability of the mid aged rat myocardium to the age-induced oxidative stress: influence of exercise training on antioxidant defense system. Free Radic Res 39:1211-7
53. Kaludercic N, Carpi A, Menabo R, Di Lisa F and Paolocci N. 2011. Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. Biochim Biophys Acta 1813:1323-32
54. Kang PT, Chen CL, Zen P, Guarini G and Chen YR. 2014. BCNU-Induced gR2 DEFECT mediates S-glutathionylation OF Complex I and RESPIRATORY uncoupling in myocardium. Biochem Pharmacol
55. Kavazis AN, Alvarez S, Talbert E, Lee Y and Powers SK. 2009. Exercise training induces a cardioprotective phenotype and alterations in cardiac subsarcolemmal and intermyofibrillar mitochondrial proteins. Am J Physiol Heart Circ Physiol 297:H144-52
56. Kloner RA and Jennings RB. 2001. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation 104:3158-67
57. Lee IM, Sesso HD and Paffenbarger RS, Jr. 2000. Physical activity and coronary heart disease risk in men: does the duration of exercise episodes predict risk? Circulation 102:981-6
58. Lee Y, Min K, Talbert EE, Kavazis AN, Smuder AJ, Willis WT and Powers SK. 2012. Exercise protects cardiac mitochondria against ischemia-reperfusion injury. Med Sci Sports Exerc 44:397-405
59. Lennon SL, Quindry J, Hamilton KL, French J, Staib J, Mehta JL and Powers SK. 2004. Loss of exercise-induced cardioprotection after cessation of exercise. J Appl Physiol (1985) 96:1299-305
60. Liu X, Miller MJ, Joshi MS, Sadowska-Krowicka H, Clark DA and Lancaster JR, Jr. 1998. Diffusion- limited reaction of free nitric oxide with erythrocytes. J Biol Chem 273:18709-13
61. Maggirwar SB, Dhanraj DN, Somani SM and Ramkumar V. 1994. Adenosine acts as an endogenous activator of the cellular antioxidant defense system. Biochem Biophys Res Commun 201:508-15
62. McCord JM. 1985. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312:159-63
63. Michel MC, Harding SE and Bond RA. 2011. Are there functional beta(3)-adrenoceptors in the human heart? Br J Pharmacol 162:817-22
64. Michelsen MM, Stottrup NB, Schmidt MR, Lofgren B, Jensen RV, Tropak M, St-Michel EJ, Redington AN and Botker HE. 2012. Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor. Basic Res Cardiol 107:260
65. Misra MK, Sarwat M, Bhakuni P, Tuteja R and Tuteja N. 2009. Oxidative stress and ischemic myocardial syndromes. Med Sci Monit 15:RA209-219
66. Mora S, Cook N, Buring JE, Ridker PM and Lee IM. 2007. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation 116:2110-8
67. Musi N, Hirshman MF, Arad M, Xing Y, Fujii N, Pomerleau J, Ahmad F, Berul CI, Seidman JG, Tian R and Goodyear LJ. 2005. Functional role of AMP-activated protein kinase in the heart during exercise. FEBS Lett 579:2045-50
68. Napp A, Brixius K, Pott C, Ziskoven C, Boelck B, Mehlhorn U, Schwinger RH and Bloch W. 2009. Effects of the beta3-adrenergic agonist BRL 37344 on endothelial nitric oxide synthase phosphorylation and force of contraction in human failing myocardium. J Card Fail 15:57-67
69. Nelson MJ, Harris MB, Boluyt MO, Hwang HS and Starnes JW. 2011. Effect of N-2-mercaptopropionyl glycine on exercise-induced cardiac adaptations. Am J Physiol Regul Integr Comp Physiol 300:R993-R1000
70. Oberman A. 1985. Exercise and the primary prevention of cardiovascular disease. Am J Cardiol 55:10D-20D
71. Ogura Y, Iemitsu M, Naito H, Kakigi R, Kakehashi C, Maeda S and Akema T. 2011. Single bout of running exercise changes LC3-II expression in rat cardiac muscle. Biochem Biophys Res Commun 414:756-60
72. Pain T, Yang XM, Critz SD, Yue Y, Nakano A, Liu GS, Heusch G, Cohen MV and Downey JM. 2000. Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res 87:460-6
73. Powers SK, Smuder AJ, Kavazis AN and Quindry JC. 2014. Mechanisms of exercise-induced cardioprotection. Physiology (Bethesda) 29:27-38
74. Prosser BL, Ward CW and Lederer WJ. 2011. X-ROS signaling: rapid mechano-chemo transduction in heart. Science 333:1440-5
75. Quindry JC, French J, Hamilton KL, Lee Y, Selsby J and Powers S. 2010a. Exercise does not increase cyclooxygenase-2 myocardial levels in young or senescent hearts. J Physiol Sci 60:181-6
76. Quindry JC and Hamilton KL. 2013. Exercise and cardiac preconditioning against ischemia reperfusion injury. Curr Cardiol Rev 9:220-9
77. Quindry JC, Schreiber L, Hosick P, Wrieden J, Irwin JM and Hoyt E. 2010b. Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts. Am J Physiol Heart Circ Physiol 299:H175-83
78. Rahkila P, Hakala E, Alen M, Salminen K and Laatikainen T. 1988. Beta-endorphin and corticotropin release is dependent on a threshold intensity of running exercise in male endurance athletes. Life Sci 43:551-8
79. Ramires PR and Ji LL. 2001. Glutathione supplementation and training increases myocardial resistance to ischemia-reperfusion in vivo. Am J Physiol Heart Circ Physiol 281:H679-88
80. Russell RR, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ and Young LH. 2004. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J Clin Invest 114:495-503
81. Sadoshima J. 2006. Redox regulation of growth and death in cardiac myocytes. Antioxid Redox Signal 8:1621-4
82. Saini HK, Xu YJ, Zhang M, Liu PP, Kirshenbaum LA and Dhalla NS. 2005. Role of tumour necrosis factor-alpha and other cytokines in ischemia-reperfusion-induced injury in the heart. Exp Clin Cardiol 10:213-22
83. Sanchez G, Escobar M, Pedrozo Z, Macho P, Domenech R, Hartel S, Hidalgo C and Donoso P. 2008. Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible role in cardioprotection. Cardiovasc Res 77:380-6
84. Sato T, Sasaki N, O’Rourke B and Marban E. 2000. Adenosine primes the opening of mitochondrial ATP-sensitive potassium channels: a key step in ischemic preconditioning? Circulation 102:800-5
85. Schultz Je-J, Hsu AK, Nagase H and Gross GJ. 1998. TAN-67, a delta 1-opioid receptor agonist, reduces infarct size via activation of Gi/o proteins and KATP channels. Am J Physiol 274:H909-14
86. Schwarz L and Kindermann W. 1992. Changes in beta-endorphin levels in response to aerobic and anaerobic exercise. Sports Med 13:25-36
87. Sessa WC, Pritchard K, Seyedi N, Wang J and Hintze TH. 1994. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res 74:349-53
88. Springhorn JP and Claycomb WC. 1989. Preproenkephalin mRNA expression in developing rat heart and in cultured ventricular cardiac muscle cells. Biochem J 258:73-8
89. Starnes JW and Taylor RP. 2007. Exercise-induced cardioprotection: endogenous mechanisms. Med Sci Sports Exerc 39:1537-43
90. Steinberg SF. 1999. The molecular basis for distinct beta-adrenergic receptor subtype actions in cardiomyocytes. Circ Res 85:1101-11
91. Sukhodub A, Jovanovic S, Du Q, Budas G, Clelland AK, Shen M, Sakamoto K, Tian R and Jovanovic A. 2007. AMP-activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ATP-sensitive K(+) channels. J Cell Physiol 210:224-36
92. Tavernier G, Toumaniantz G, Erfanian M, Heymann MF, Laurent K, Langin D and Gauthier C. 2003. beta3-Adrenergic stimulation produces a decrease of cardiac contractility ex vivo in mice over- expressing the human beta3-adrenergic receptor. Cardiovasc Res 59:288-96
93. Taylor RP, Harris MB and Starnes JW. 1999. Acute exercise can improve cardioprotection without increasing heat shock protein content. Am J Physiol 276:H1098-102
94. Taylor RP, Olsen ME and Starnes JW. 2007. Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart. Am J Physiol Heart Circ Physiol 292:H601-7
95. Taylor RP and Starnes JW. 2012. Reactive oxygen species are not a required trigger for exercise-induced late preconditioning in the rat heart. Am J Physiol Regul Integr Comp Physiol 303:R968-74
96. Tsutsui H, Kinugawa S and Matsushima S. 2011. Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol 301:H2181-90
97. van den Brink OW, Delbridge LM, Rosenfeldt FL, Penny D, Esmore DS, Quick D, Kaye DM and Pepe S. 2003. Endogenous cardiac opioids: enkephalins in adaptation and protection of the heart. Heart Lung Circ 12:178-87
98. Vegh A and Parratt JR. 2005. A common mechanism in the protective effects of preconditioning, cardiac pacing and physical exercise against ischemia and reperfusion-induced arrhythmias. Exp Clin Cardiol 10:200-5
99. Venditti P and Di Meo S. 1996. Antioxidants, tissue damage, and endurance in trained and untrained young male rats. Arch Biochem Biophys 331:63-8
100. Vidal M, Wieland T, Lohse MJ and Lorenz K. 2012. Beta-Adrenergic receptor stimulation causes cardiac hypertrophy via a Gbetagamma/Erk-dependent pathway. Cardiovasc Res 96:255-64
101. Wang J, Wolin MS and Hintze TH. 1993. Chronic exercise enhances endothelium-mediated dilation of epicardial coronary artery in conscious dogs. Circ Res 73:829-38
102. Ward CW, Prosser BL and Lederer WJ. 2014. Mechanical stretch-induced activation of ROS/RNS signaling in striated muscle. Antioxid Redox Signal 20:929-36
103. Watkinson WP, Foley DH, Rubio R and Berne RM. 1979. Myocardial adenosine formation with increased cardiac performance in the dog. Am J Physiol 236:H13-21
104. Webb A, Bond R, McLean P, Uppal R, Benjamin N and Ahluwalia A. 2004. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci U S A 101:13683-8
105. Weil J, Zolk O, Griepentrog J, Wenzel U, Zimmermann WH and Eschenhagen T. 2006. Alterations of the preproenkephalin system in cardiac hypertrophy and its role in atrioventricular conduction. Cardiovasc Res 69:412-22
106. Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T and Hori M. 1999. Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med 189:1699-706
107. Zhang QJ, McMillin SL, Tanner JM, Palionyte M, Abel ED and Symons JD. 2009. Endothelial nitric oxide synthase phosphorylation in treadmill-running mice: role of vascular signalling kinases. J Physiol 587:3911-20
108. Zhou M, Widmer RJ, Xie W, Jimmy Widmer A, Miller MW, Schroeder F, Parker JL and Heaps CL. 2010. Effects of exercise training on cellular mechanisms of endothelial nitric oxide synthase regulation in coronary arteries after chronic occlusion. Am J Physiol Heart Circ Physiol 298:H1857-69
109. Zweier JL, Wang P, Samouilov A and Kuppusamy P. 1995. Enzyme-independent formation of nitric oxide in biological tissues. Nat Med 1:804-9