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Cardioprotection in females: a role for nitric oxide and altered gene expression

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Abstract

A number of epidemiological and animal studies have suggested a cardioprotective role for estrogen. This review will focus on the cardioprotective role of estrogen in ischemia-reperfusion injury. Estrogen binding to receptors can lead to altered gene expression and estrogen has been shown to induce expression of a number of genes that have been suggested to be important in cardioprotection. Estrogen is reported to increase expression of the plasma membrane glucose transporter GLUT4 and to increase carbohydrate metabolism. Estrogen has also been reported to increase mitochondrial biogenesis and to alter mitochondrial generation of reactive oxygen species. Estrogen results in upregulation of cardiac eNOS and nNOS, which have been shown previously to be important mediators of cardioprotection. Nitric oxide has been shown to result in S-nitrosylation and inhibition of the L-type calcium channel, thereby reducing calcium loading during ischemia. Nitric oxide has also been reported to inhibit complex I and inhibition of complex I has been reported to reduce activation of the mitochondrial permeability transition pore. Nitric oxide has been shown to result in activation of the mitochondrial KATP channel, which has been shown to be involved in cardioprotection. Estrogen can also activate rapid non-genomic pathways that activate cardioprotective-signaling pathways such as the phosphatidylinositol-3-kinase (PI-3 kinase) pathway which has also been shown to initiate protection. Taken together, estrogen by genomic and non-genomic pathways can result in the initiation of a number of signaling pathways that enhance cardioprotection.

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References

  1. Barrett-Connor E (1997) Sex differences in coronary heart disease. Why are women so superior? The 1995 Ancel Keys Lecture. Circulation 95:252–264

    PubMed  CAS  Google Scholar 

  2. Crabbe DL, Dipla K, Ambati S, Zafeiridis A, Gaughan JP, Houser SR, Margulies KB (2003) Gender differences in post-infarction hypertrophy in end-stage failing hearts. J Am Coll Cardiol 41:300–306

    Article  PubMed  Google Scholar 

  3. Hayward CS, Kelly RP, Collins P (2000) The roles of gender, the menopause and hormone replacement on cardiovascular function. Cardiovasc Res 46:28–49

    Article  PubMed  CAS  Google Scholar 

  4. Mendelsohn ME, Karas RH (1999) The protective effects of estrogen on the cardiovascular system. N Engl J Med 340:1801–1811

    Article  PubMed  CAS  Google Scholar 

  5. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. Jama 288:321–333

    Article  PubMed  CAS  Google Scholar 

  6. Mendelsohn ME, Karas RH (2005) Molecular and cellular basis of cardiovascular gender differences. Science 308:1583–1587

    Article  PubMed  CAS  Google Scholar 

  7. Turgeon JL, Carr MC, Maki PM, Mendelsohn ME, Wise PM (2006) Complex actions of sex steroids in adipose tissue, the cardiovascular system, and brain: Insights from basic science and clinical studies. Endocr Rev 27:575–605

    Article  PubMed  CAS  Google Scholar 

  8. Ouyang P, Michos ED, Karas RH (2006) Hormone replacement therapy and the cardiovascular system lessons learned and unanswered questions. J Am Coll Cardiol 47:1741–1753

    Article  PubMed  CAS  Google Scholar 

  9. Lindberg MK, Moverare S, Skrtic S, Gao H, Dahlman-Wright K, Gustafsson JA, Ohlsson C (2003) Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a “ying yang” relationship between ERalpha and ERbeta in mice. Mol Endocrinol 17:203–208

    Article  PubMed  CAS  Google Scholar 

  10. Wang JM, Irwin RW, Brinton RD (2006) Activation of estrogen receptor alpha increases and estrogen receptor beta decreases apolipoprotein E expression in hippocampus in vitro and in vivo. Proc Natl Acad Sci USA 103:16983–16988

    Article  PubMed  CAS  Google Scholar 

  11. Deroo BJ, Korach KS (2006) Estrogen receptors and human disease. J Clin Invest 116:561–570

    Article  PubMed  CAS  Google Scholar 

  12. Sanchez R, Nguyen D, Rocha W, White JH, Mader S (2002) Diversity in the mechanisms of gene regulation by estrogen receptors. Bioessays 24:244–254

    Article  PubMed  CAS  Google Scholar 

  13. Curtis SW, Washburn T, Sewall C, DiAugustine R, Lindzey J, Couse JF, Korach KS (1996) Physiological coupling of growth factor and steroid receptor signaling pathways: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor. Proc Natl Acad Sci USA 93:12626–12630

    Article  PubMed  CAS  Google Scholar 

  14. Kalaitzidis D, Gilmore TD (2005) Transcription factor cross-talk: the estrogen receptor and NF-kappaB. Trends Endocrinol Metab 16:46–52

    Article  PubMed  CAS  Google Scholar 

  15. Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407:538–541

    Article  PubMed  CAS  Google Scholar 

  16. Filardo EJ, Thomas P (2005) GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release. Trends Endocrinol Metab 16:362–367

    Article  PubMed  CAS  Google Scholar 

  17. Bae S, Zhang L (2005) Gender differences in cardioprotection against ischemia/reperfusion injury in adult rat hearts: focus on Akt and protein kinase C signaling. J Pharmacol Exp Ther 315:1125–1135

    Article  PubMed  CAS  Google Scholar 

  18. Wang M, Crisostomo P, Wairiuko GM, Meldrum DR (2006) Estrogen receptor-alpha mediates acute myocardial protection in females. Am J Physiol Heart Circ Physiol 290:H2204–2209

    Article  PubMed  CAS  Google Scholar 

  19. Przyklenk K, Ovize M, Bauer B, Kloner RA (1995) Gender does not influence acute myocardial infarction in adult dogs. Am Heart J 129:1108–1113

    Article  PubMed  CAS  Google Scholar 

  20. Li Y, Kloner RA (1995) Is There a Gender Difference in Infarct Size and Arrhythmias Following Experimental Coronary Occlusion and Reperfusion? J Thromb Thrombolysis 2:221–225

    PubMed  Google Scholar 

  21. Cross HR, Lu L, Steenbergen C, Philipson KD, Murphy E (1998) Overexpression of the cardiac Na+/Ca2+ exchanger increases susceptibility to ischemia/reperfusion injury in male, but not female, transgenic mice. Circ Res 83:1215–1223

    PubMed  CAS  Google Scholar 

  22. Cross HR, Kranias EG, Murphy E, Steenbergen C (2003) Ablation of PLB exacerbates ischemic injury to a lesser extent in female than male mice: protective role of NO. Am J Physiol Heart Circ Physiol 284:H683–690

    PubMed  CAS  Google Scholar 

  23. Cross HR, Steenbergen C, Lefkowitz RJ, Koch WJ, Murphy E (1999) Overexpression of the cardiac beta(2)-adrenergic receptor and expression of a beta-adrenergic receptor kinase-1 (betaARK1) inhibitor both increase myocardial contractility but have differential effects on susceptibility to ischemic injury. Circ Res 85:1077–1084

    PubMed  CAS  Google Scholar 

  24. Cross HR, Murphy E, Steenbergen C (2002) Ca(2+) loading and adrenergic stimulation reveal male/female differences in susceptibility to ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 283:H481–489

    PubMed  CAS  Google Scholar 

  25. Gabel SA, Walker VR, London RE, Steenbergen C, Korach KS, Murphy E (2005) Estrogen receptor beta mediates gender differences in ischemia/reperfusion injury. J Mol Cell Cardiol 38:289–297

    Article  PubMed  CAS  Google Scholar 

  26. Kam KW, Qi JS, Chen M, Wong TM (2004) Estrogen reduces cardiac injury and expression of beta1-adrenoceptor upon ischemic insult in the rat heart. J Pharmacol Exp Ther 309:8–15

    Article  PubMed  CAS  Google Scholar 

  27. Booth EA, Obeid NR, Lucchesi BR (2005) Activation of estrogen receptor-alpha protects the in vivo rabbit heart from ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 289:H2039–2047

    Article  PubMed  CAS  Google Scholar 

  28. Das B, Sarkar C (2006) Similarities between ischemic preconditioning and 17beta-estradiol mediated cardiomyocyte KATP channel activation leading to cardioprotective and antiarrhythmic effects during ischemia/reperfusion in the intact rabbit heart. J Cardiovasc Pharmacol 47:277–286

    Article  PubMed  CAS  Google Scholar 

  29. Hale SL, Birnbaum Y, Kloner RA (1996) beta-Estradiol, but not alpha-estradiol, reduced myocardial necrosis in rabbits after ischemia and reperfusion. Am Heart J 132:258–262

    Article  PubMed  CAS  Google Scholar 

  30. Booth EA, Marchesi M, Kilbourne EJ, Lucchesi BR (2003) 17Beta-estradiol as a receptor-mediated cardioprotective agent. J Pharmacol Exp Ther 307:395–401

    Article  PubMed  CAS  Google Scholar 

  31. Sbarouni E, Iliodromitis EK, Bofilis E, Kyriakides ZS, Kremastinos DT (1998) Short-term estrogen reduces myocardial infarct size in oophorectomized female rabbits in a dose-dependent manner. Cardiovasc Drugs Ther 12:457–462

    Article  PubMed  CAS  Google Scholar 

  32. Sbarouni E, Iliodromitis EK, Bofilis E, Kyriakides ZS, Kremastinos DT (2003) Estrogen alone or combined with medroxyprogesterone but not raloxifene reduce myocardial infarct size. Eur J Pharmacol 467:163–168

    Article  PubMed  CAS  Google Scholar 

  33. Lee TM, Su SF, Tsai CC, Lee YT, Tsai CH (2000) Cardioprotective effects of 17 beta-estradiol produced by activation ofmitochondrial ATP-sensitive K(+)Channels in canine hearts. J Mol Cell Cardiol 32:1147–1158

    Article  PubMed  CAS  Google Scholar 

  34. Zhai P, Eurell TE, Cooke PS, Lubahn DB, Gross DR (2000) Myocardial ischemia-reperfusion injury in estrogen receptor-alpha knockout and wild-type mice. Am J Physiol Heart Circ Physiol 278:H1640–1647

    PubMed  CAS  Google Scholar 

  35. Yu HP, Shimizu T, Choudhry MA, Hsieh YC, Suzuki T, Bland KI, Chaudry IH (2006) Mechanism of cardioprotection following trauma-hemorrhagic shock by a selective estrogen receptor-beta agonist: up-regulation of cardiac heat shock factor-1 and heat shock proteins. J Mol Cell Cardiol 40:185–194

    Article  PubMed  CAS  Google Scholar 

  36. Nikolic, I., Liu, D., Bell, J., Collins, J., Steenbergen, C., and Murphy, E (2007) Treatment with an estrogen receptor beta selective agonist is cardioprotective. J Molec Cellular Cardiol 42:769–780

    Article  CAS  Google Scholar 

  37. Hsieh YC, Choudhry MA, Yu HP, Shimizu T, Yang S, Suzuki T, Chen J, Bland KI, Chaudry IH (2006) Inhibition of cardiac PGC-1alpha expression abolishes ERbeta agonist-mediated cardioprotection following trauma-hemorrhage. Faseb J 20:1109–1117

    Article  PubMed  CAS  Google Scholar 

  38. Mendelsohn ME (2000) Nongenomic, ER-mediated activation of endothelial nitric oxide synthase: how does it work? What does it mean? Circ Res 87:956–960

    PubMed  CAS  Google Scholar 

  39. Nuedling S, Karas RH, Mendelsohn ME, Katzenellenbogen JA, Katzenellenbogen BS, Meyer R, Vetter H, Grohe C (2001) Activation of estrogen receptor beta is a prerequisite for estrogen-dependent upregulation of nitric oxide synthases in neonatal rat cardiac myocytes. FEBS Lett 502:103–108

    Article  PubMed  CAS  Google Scholar 

  40. Sun J, Picht E, Ginsburg KS, Bers DM, Steenbergen C, Murphy E (2006) Hypercontractile female hearts exhibit increased S-nitrosylation of the L-type Ca2+ channel alpha1 subunit and reduced ischemia/reperfusion injury. Circ Res 98:403–411

    Article  PubMed  CAS  Google Scholar 

  41. Chen J, Petranka J, Yamamura K, London RE, Steenbergen C, Murphy E (2003) Gender differences in sarcoplasmic reticulum calcium loading after isoproterenol. Am J Physiol Heart Circ Physiol 285:H2657–2662

    PubMed  CAS  Google Scholar 

  42. Jones SP, Bolli R (2006) The ubiquitous role of nitric oxide in cardioprotection. J Mol Cell Cardiol 40:16–23

    Article  PubMed  CAS  Google Scholar 

  43. Costa AD, Garlid KD, West IC, Lincoln TM, Downey JM, Cohen MV, Critz SD (2005) Protein kinase G transmits the cardioprotective signal from cytosol to mitochondria. Circ Res 97:329–336

    Article  PubMed  CAS  Google Scholar 

  44. Burwell LS, Nadtochiy SM, Tompkins AJ, Young S, Brookes PS (2006) Direct evidence for S-nitrosation of mitochondrial complex I. Biochem J 394:627–634

    Article  PubMed  CAS  Google Scholar 

  45. Martin C, Schulz R, Post H, Gres P, Heusch G (2003) Effect of NO synthase inhibition on myocardial metabolism during moderate ischemia. Am J Physiol Heart Circ Physiol 284:H2320–2324

    PubMed  CAS  Google Scholar 

  46. Recchia FA, Osorio JC, Chandler MP, Xu X, Panchal AR, Lopaschuk GD, Hintze TH, Stanley WC (2002) Reduced synthesis of NO causes marked alterations in myocardial substrate metabolism in conscious dogs. Am J Physiol Endocrinol Metab 282:E197–206

    PubMed  CAS  Google Scholar 

  47. Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonello C, Sciorati C, Bracale R, Valerio A, Francolini M, Moncada S, Carruba MO (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299:896–899

    Article  PubMed  CAS  Google Scholar 

  48. Otsuki M, Gao H, Dahlman-Wright K, Ohlsson C, Eguchi N, Urade Y, Gustafsson JA (2003) Specific regulation of lipocalin-type prostaglandin D synthase in mouse heart by estrogen receptor beta. Mol Endocrinol 17:1844–1855

    Article  PubMed  CAS  Google Scholar 

  49. Cappola TP, Cope L, Cernetich A, Barouch LA, Minhas K, Irizarry RA, Parmigiani G, Durrani S, Lavoie T, Hoffman EP, Ye SQ, Garcia JG, Hare JM (2003) Deficiency of different nitric oxide synthase isoforms activates divergent transcriptional programs in cardiac hypertrophy. Physiol Genomics 14:25–34

    PubMed  CAS  Google Scholar 

  50. Miyazaki M, Jacobson MJ, Man WC, Cohen P, Asilmaz E, Friedman JM, Ntambi JM (2003) Identification and characterization of murine SCD4, a novel heart-specific stearoyl-CoA desaturase isoform regulated by leptin and dietary factors. J Biol Chem 278:33904–33911

    Article  PubMed  CAS  Google Scholar 

  51. Dobrzyn A, Ntambi JM (2004) The role of stearoyl-CoA desaturase in body weight regulation. Trends Cardiovasc Med 14:77–81

    Article  PubMed  CAS  Google Scholar 

  52. Lopez D, Sanchez MD, Shea-Eaton W, McLean MP (2002) Estrogen activates the high-density lipoprotein receptor gene via binding to estrogen response elements and interaction with sterol regulatory element binding protein-1A. Endocrinology 143:2155–2168

    Article  PubMed  CAS  Google Scholar 

  53. Donthi RV, Ye G, Wu C, McClain DA, Lange AJ, Epstein PN (2004) Cardiac expression of kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase inhibits glycolysis, promotes hypertrophy, impairs myocyte function, and reduces insulin sensitivity. J Biol Chem 279:48085–48090

    Article  PubMed  CAS  Google Scholar 

  54. Chung TH, Wang SM, Wu JC (2004) 17beta-estradiol reduces the effect of metabolic inhibition on gap junction intercellular communication in rat cardiomyocytes via the estrogen receptor. J Mol Cell Cardiol 37:1013–1022

    Article  PubMed  CAS  Google Scholar 

  55. Yu W, Dahl G, Werner R (1994) The connexin43 gene is responsive to oestrogen. Proc Biol Sci 255:125–132

    Article  PubMed  CAS  Google Scholar 

  56. Too CK, Giles A, Wilkinson M (1999) Estrogen stimulates expression of adenine nucleotide translocator ANT1 messenger RNA in female rat hearts. Mol Cell Endocrinol 150:161–167

    Article  PubMed  CAS  Google Scholar 

  57. Voss MR, Stallone JN, Li M, Cornelussen RN, Knuefermann P, Knowlton AA (2003) Gender differences in the expression of heat shock proteins: the effect of estrogen. Am J Physiol Heart Circ Physiol 285:H687–692

    PubMed  CAS  Google Scholar 

  58. Hsieh YC, Yu HP, Suzuki T, Choudhry MA, Schwacha MG, Bland KI, Chaudry IH (2006) Upregulation of mitochondrial respiratory complex IV by estrogen receptor-beta is critical for inhibiting mitochondrial apoptotic signaling and restoring cardiac functions following trauma-hemorrhage. J Mol Cell Cardiol 41:511–521

    Article  PubMed  CAS  Google Scholar 

  59. Barros RP, Machado UF, Warner M, Gustafsson JA (2006) Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha. Proc Natl Acad Sci USA 103:1605–1608

    Article  PubMed  CAS  Google Scholar 

  60. Pedram A, Razandi M, Aitkenhead M, Levin ER (2005) Estrogen inhibits cardiomyocyte hypertrophy in vitro. Antagonism of calcineurin-related hypertrophy through induction of MCIP1. J Biol Chem 280:26339–26348

    Article  PubMed  CAS  Google Scholar 

  61. Boengler K, Schulz R, Heusch G (2006) Connexin 43 signalling and cardioprotection. Heart 92:1724–1727

    Article  PubMed  CAS  Google Scholar 

  62. Shamaei-Tousi A, Halcox JP, Henderson B (2007) Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease. Cardiovasc Res 74:19–28

    Article  PubMed  CAS  Google Scholar 

  63. Justo R, Boada J, Frontera M, Oliver J, Bermudez J, Gianotti M (2005) Gender dimorphism in rat liver mitochondrial oxidative metabolism and biogenesis. Am J Physiol Cell Physiol 289:C372–378

    Article  PubMed  CAS  Google Scholar 

  64. Duckles SP, Krause DN, Stirone C, Procaccio V (2006) Estrogen and mitochondria: a new paradigm for vascular protection? Mol Interv 6:26–35

    Article  PubMed  Google Scholar 

  65. Stirone C, Duckles SP, Krause DN, Procaccio V (2005) Estrogen increases mitochondrial efficiency and reduces oxidative stress in cerebral blood vessels. Mol Pharmacol 68:959–965

    Article  PubMed  CAS  Google Scholar 

  66. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, Moncada S, Carruba MO (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314–317

    Article  PubMed  CAS  Google Scholar 

  67. Alcendor RR, Kirshenbaum LA, Imai S, Vatner SF, Sadoshima J (2004) Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circ Res 95:971–980

    Article  PubMed  CAS  Google Scholar 

  68. Yan L, Ge H, Li H, Lieber SC, Natividad F, Resuello RR, Kim SJ, Akeju S, Sun A, Loo K, Peppas AP, Rossi F, Lewandowski ED, Thomas AP, Vatner SF, Vatner DE (2004) Gender-specific proteomic alterations in glycolytic and mitochondrial pathways in aging monkey hearts. J Mol Cell Cardiol 37:921–929

    Article  PubMed  CAS  Google Scholar 

  69. Pedram A, Razandi M, Wallace DC, Levin ER (2006) Functional estrogen receptors in the mitochondria of breast cancer cells. Mol Biol Cell 17:2125–2137

    Article  PubMed  CAS  Google Scholar 

  70. Yang SH, Liu R, Perez EJ, Wen Y, Stevens SM, Jr Valencia T, Brun-Zinkernagel AM, Prokai L, Will Y, Dykens J, Koulen P, Simpkins JW (2004) Mitochondrial localization of estrogen receptor beta. Proc Natl Acad Sci USA 101:4130–4135

    Article  PubMed  CAS  Google Scholar 

  71. Schwend T, Gustafsson JA (2006) False positives in MALDI-TOF detection of ERbeta in mitochondria. Biochem Biophys Res Commun 343:707–711

    Article  PubMed  CAS  Google Scholar 

  72. Kanaya AM, Herrington D, Vittinghoff E, Lin F, Grady D, Bittner V, Cauley JA, Barrett-Connor E (2003) Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 138:1–9

    PubMed  CAS  Google Scholar 

  73. Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS (2000) Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci USA 97:12729–12734

    Article  PubMed  CAS  Google Scholar 

  74. Naaz A, Zakroczymski M, Heine P, Taylor J, Saunders P, Lubahn D, Cooke PS (2002) Effect of ovariectomy on adipose tissue of mice in the absence of estrogen receptor alpha (ERalpha): a potential role for estrogen receptor beta (ERbeta). Horm Metab Res 34:758–763

    Article  PubMed  CAS  Google Scholar 

  75. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS (1994) Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 331:1056–1061

    Article  PubMed  CAS  Google Scholar 

  76. Lopaschuk GD (1998) Treating ischemic heart disease by pharmacologically improving cardiac energy metabolism. Am J Cardiol 82:14K–17K

    Article  PubMed  CAS  Google Scholar 

  77. Apstein CS (2000) Increased glycolytic substrate protection improves ischemic cardiac dysfunction and reduces injury. Am Heart J 139:S107–114

    Article  PubMed  CAS  Google Scholar 

  78. Lopaschuk GD, Barr R, Thomas PD, Dyck JR (2003) Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme a thiolase. Circ Res 93:e33–37

    Article  PubMed  CAS  Google Scholar 

  79. Wahr JA, Olszanski D, Childs KF, Bolling SF (1996) Dichloroacetate enhanced myocardial functional recovery post-ischemia: ATP and NADH recovery. J Surg Res 63:220–224

    Article  PubMed  CAS  Google Scholar 

  80. Saeedi R, Wambolt RB, Parsons H, Antler C, Leong HS, Keller A, Dunaway GA, Popov KM, Allard MF (2006) Gender and post-ischemic recovery of hypertrophied rat hearts. BMC Cardiovasc Disord 6:8

    Article  PubMed  CAS  Google Scholar 

  81. Kurzelewski M, Duda M, Stanley WC, Boemke W, Beresewicz A (2004) Nitric oxide synthase inhibition and elevated endothelin increase oxygen consumption but do not affect glucose and palmitate oxidation in the isolated rat heart. J Physiol Pharmacol 55:27–38

    PubMed  CAS  Google Scholar 

  82. Lei B, Matsuo K, Labinskyy V, Sharma N, Chandler MP, Ahn A, Hintze TH, Stanley WC, Recchia FA (2005) Exogenous nitric oxide reduces glucose transporters translocation and lactate production in ischemic myocardium in vivo. Proc Natl Acad Sci USA 102:6966–6971

    Article  PubMed  CAS  Google Scholar 

  83. Li J, Hu X, Selvakumar P, Russell RR, 3rd Cushman SW, Holman GD, Young LH (2004) Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab 287:E834–841

    Article  PubMed  CAS  Google Scholar 

  84. Sasaki N, Sato T, Ohler A, O’Rourke B, Marban E (2000) Activation of mitochondrial ATP-dependent potassium channels by nitric oxide. Circulation 101:439–445

    PubMed  CAS  Google Scholar 

  85. Fontaine E, Eriksson O, Ichas F, Bernardi P (1998) Regulation of the permeability transition pore in skeletal muscle mitochondria. Modulation by electron flow through the respiratory chain complex i. J Biol Chem 273:12662–12668

    Article  PubMed  CAS  Google Scholar 

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  1. Head Cardiac Physiology Section, Vascular Medicine Branch, NHLBI, Building 10, Room 7N112, 10 Center Drive, Bethesda, MD, 20892, USA

    Elizabeth Murphy

  2. Department of Pathology, Johns Hopkins Medical Institute, Baltimore, MD, USA

    Charles Steenbergen

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Correspondence to Elizabeth Murphy.

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Murphy, E., Steenbergen, C. Cardioprotection in females: a role for nitric oxide and altered gene expression. Heart Fail Rev 12, 293–300 (2007). https://doi.org/10.1007/s10741-007-9035-0

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