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Melatonin, mitochondria and hypertension

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Abstract

Melatonin, due to its multiple means and mechanisms of action, plays a fundamental role in the regulation of the organismal physiology by fine tunning several functions. The cardiovascular system is an important site of action as melatonin regulates blood pressure both by central and peripheral interventions, in addition to its relation with the renin–angiotensin system. Besides, the systemic management of several processes, melatonin acts on mitochondria regulation to maintain a healthy cardiovascular system. Hypertension affects target organs in different ways and cellular energy metabolism is frequently involved due to mitochondrial alterations that include a rise in reactive oxygen species production and an ATP synthesis decrease. The discussion that follows shows the role played by melatonin in the regulation of mitochondrial physiology in several levels of the cardiovascular system, including brain, heart, kidney, blood vessels and, particularly, regulating the renin–angiotensin system. This discussion shows the putative importance of using melatonin as a therapeutic tool involving its antioxidant potential and its action on mitochondrial physiology in the cardiovascular system.

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References

  1. Reiter RJ (1991) Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 12:151–180

    Article  CAS  PubMed  Google Scholar 

  2. Reiter RJ (1991) Melatonin: the chemical expression of darkness. Mol Cell Endocrinol 79:C153–C158

    Article  CAS  PubMed  Google Scholar 

  3. Reiter RJ, Tan DX, Galano A (2014) Melatonin: exceeding expectations. Physiol (Bethesda) 29:325–333

    CAS  Google Scholar 

  4. Victor VM, Rocha M (2007) Targeting antioxidants to mitochondria: a potential new therapeutic strategy for cardiovascular diseases. Curr Pharm Des 13:845–863

    Article  CAS  PubMed  Google Scholar 

  5. Zanoboni A, Forni A, Zanoboni-Muciaccia W, Zanussi C (1978) Effect of pinealectomy on arterial blood pressure and food and water intake in the rat. J Endocrinol Invest 1:125–130

    Article  CAS  PubMed  Google Scholar 

  6. Zanoboni A, Zanoboni-Muciaccia W (1967) Experimental hypertension in pinealectomized rats. Life Sci 6:2327–2331

    Article  CAS  PubMed  Google Scholar 

  7. Holmes SW, Sugden D (1976) Proceedings: the effect of melatonin on pinealectomy-induced hypertension in the rat. Br J Pharmacol 56:360P–361P

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Campos LA, Cipolla-Neto J, Michelini LC (2013) Melatonin modulates baroreflex control via area postrema. Brain Behav 3:171–177

    Article  PubMed  PubMed Central  Google Scholar 

  9. Pechanova O, Paulis L, Simko F (2014) Peripheral and central effects of melatonin on blood pressure regulation. Int J Mol Sci 15:17920–17937

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Simko F, Baka T, Paulis L, Reiter RJ (2016) Elevated heart rate and nondipping heart rate as potential targets for melatonin: a review. J Pineal Res 61:127–137

    Article  CAS  PubMed  Google Scholar 

  11. Viswanathan M, Laitinen JT, Saavedra JM (1993) Vascular melatonin receptors. Biol Signals 2:221–227

    Article  CAS  PubMed  Google Scholar 

  12. Baltatu O, Afeche SC, Jose dos Santos SH, Campos LA, Barbosa R, Michelini LC, Bader M, Cipolla-Neto J (2002) Locally synthesized angiotensin modulates pineal melatonin generation. J Neurochem 80:328–334

    Article  CAS  PubMed  Google Scholar 

  13. Campos LA, Cipolla-Neto J, Amaral FG, Michelini LC, Bader M, Baltatu OC (2013) The angiotensin-melatonin axis. Int J Hypertens 2013:521783

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Reiter RJ, Tan DX, Korkmaz A (2009) The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens Suppl 27:S17–S20

    Article  CAS  PubMed  Google Scholar 

  15. Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM (2004) Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 43:192–197

    Article  CAS  PubMed  Google Scholar 

  16. Cagnacci A, Cannoletta M, Renzi A, Baldassari F, Arangino S, Volpe A (2005) Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens 18:1614–1618

    Article  CAS  PubMed  Google Scholar 

  17. Jonas M, Garfinkel D, Zisapel N, Laudon M, Grossman E (2003) Impaired nocturnal melatonin secretion in non-dipper hypertensive patients. Blood Press 12:19–24

    PubMed  Google Scholar 

  18. Hermida RC, Ayala DE, Mojon A, Fernandez JR (2010) Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int 27:1629–1651

    Article  PubMed  Google Scholar 

  19. Tain YL, Huang LT, Chan JY (2014) Transcriptional regulation of programmed hypertension by melatonin: an epigenetic perspective. Int J Mol Sci 15:18484–18495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mensah GA (2016) Hypertension and target organ damage: don’t believe everything you think! Ethn Dis 26:275–278

    Article  PubMed  PubMed Central  Google Scholar 

  21. Neves MF, Virdis A, Oigman W (2012) Target organ damage in hypertension. Int J Hypertens 2012:454508

    PubMed  PubMed Central  Google Scholar 

  22. Campos LA, Bader M, Baltatu OC (2011) Brain Renin-Angiotensin system in hypertension, cardiac hypertrophy, and heart failure. Front Physiol 2:115

    PubMed  Google Scholar 

  23. Nadruz W (2015) Myocardial remodeling in hypertension. J Hum Hypertens 29:1–6

    Article  CAS  PubMed  Google Scholar 

  24. Watson B Jr (2003) Genetics of the kidney and hypertension. Curr Hypertens Rep 5:273–276

    Article  PubMed  Google Scholar 

  25. Nasrallah CM, Horvath TL (2014) Mitochondrial dynamics in the central regulation of metabolism. Nat Rev Endocrinol 10:650–658

    Article  CAS  PubMed  Google Scholar 

  26. Lahera V, de Las Heras N, Lopez-Farre A, Manucha W, Ferder L (2017) Role of mitochondrial dysfunction in hypertension and obesity. Curr Hypertens Rep 19:11

    Article  PubMed  CAS  Google Scholar 

  27. Vasquez-Trincado C, Garcia-Carvajal I, Pennanen C, Parra V, Hill JA, Rothermel BA, Lavandero S (2016) Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol 594:509–525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Goto Y, Yoshikane H, Honda M, Morioka S, Yamori Y, Moriyama K (1990) Three-dimensional observation on sarcoplasmic reticulum and caveolae in myocardium of spontaneously hypertensive rats. J Submicrosc Cytol Pathol 22:535–542

    CAS  PubMed  Google Scholar 

  29. Rosca MG, Tandler B, Hoppel CL (2013) Mitochondria in cardiac hypertrophy and heart failure. J Mol Cell Cardiol 55:31–41

    Article  CAS  PubMed  Google Scholar 

  30. Goldenthal MJ (2016) Mitochondrial involvement in myocyte death and heart failure. Heart Fail Rev 21:137–155

    Article  CAS  PubMed  Google Scholar 

  31. Hall AR, Burke N, Dongworth RK, Hausenloy DJ (2014) Mitochondrial fusion and fission proteins: novel therapeutic targets for combating cardiovascular disease. Br J Pharmacol 171:1890–1906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shen W, Asai K, Uechi M, Mathier MA, Shannon RP, Vatner SF, Ingwall JS (1999) Progressive loss of myocardial ATP due to a loss of total purines during the development of heart failure in dogs: a compensatory role for the parallel loss of creatine. Circulation 100(20):2113–2118

    Article  CAS  PubMed  Google Scholar 

  33. Sovari AA (2016) Cellular and molecular mechanisms of arrhythmia by oxidative stress. Cardiol Res Pract 2016:9656078

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tse G, Yan BP, Chan YW, Tian XY, Huang Y (2016) Reactive oxygen species, endoplasmic reticulum stress and mitochondrial dysfunction: the link with cardiac arrhythmogenesis. Front Physiol 7:313

    PubMed  PubMed Central  Google Scholar 

  35. Marin-Garcia J, Akhmedov AT (2016) Mitochondrial dynamics and cell death in heart failure. Heart Fail Rev 21:123–136

    Article  CAS  PubMed  Google Scholar 

  36. Ingwall JS, Atkinson DE, Clarke K, Fetters JK (1990) Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocardium. Eur Heart J 11(Suppl B):108–115

    Article  CAS  PubMed  Google Scholar 

  37. Atlante A, Seccia TM, Pierro P, Vulpis V, Marra E, Pirrelli A, Passarella S (1998) ATP synthesis and export in heart left ventricle mitochondria from spontaneously hypertensive rat. Int J Mol Med 1:709–716

    CAS  PubMed  Google Scholar 

  38. Dart CH Jr, Holloszy JO (1969) Hypertrophied non-failing rat heart; partial biochemical characterization. Circ Res 25:245–253

    Article  CAS  PubMed  Google Scholar 

  39. McCallister BD, Brown AL Jr (1969) A quantitative study of myocardial mitochondria in experimental cardiac hypertrophy. Ann N Y Acad Sci 156:469–479

    Article  CAS  PubMed  Google Scholar 

  40. Dowlatshahi K, Hunt AC (1969) Electron microscopical findings in hypertrophied human ventricle. Br Heart J 31:200–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Jullig M, Hickey AJ, Chai CC, Skea GL, Middleditch MJ, Costa S, Choong SY, Philips AR, Cooper GJ (2008) Is the failing heart out of fuel or a worn engine running rich? A study of mitochondria in old spontaneously hypertensive rats. Proteomics 8:2556–2572

    Article  CAS  PubMed  Google Scholar 

  42. Neubauer S (2007) The failing heart—an engine out of fuel. N Engl J Med 356:1140–1151

    Article  PubMed  Google Scholar 

  43. von Hardenberg A, Maack C (2017) Mitochondrial therapies in heart failure. Handb Exp Pharmacol 243:491–514. doi:10.1007/164_2016_123

    Article  Google Scholar 

  44. Banovic MD, Ristic AD (2016) The role of mitochondrial dysfunction in heart failure and potential therapeutic targets. Curr Pharm Des 22:4752–4762

    Article  PubMed  CAS  Google Scholar 

  45. Judd E, Calhoun DA (2015) Management of hypertension in CKD: beyond the guidelines. Adv Chronic Kidney Dis 22:116–122

    Article  PubMed  PubMed Central  Google Scholar 

  46. Muntner P, Anderson A, Charleston J, Chen Z, Ford V, Makos G, O’Connor A, Perumal K, Rahman M, Steigerwalt S, Teal V, Townsend R, Weir M, Wright JT Jr, Chronic Renal Insufficiency Cohort Study I (2010) Hypertension awareness, treatment, and control in adults with CKD: results from the chronic renal insufficiency cohort (CRIC) study. Am J Kidney Dis 55:441–451

    Article  CAS  PubMed  Google Scholar 

  47. Lash JP, Go AS, Appel LJ, He J, Ojo A, Rahman M, Townsend RR, Xie D, Cifelli D, Cohan J, Fink JC, Fischer MJ, Gadegbeku C, Hamm LL, Kusek JW, Landis JR, Narva A, Robinson N, Teal V, Feldman HI, Chronic Renal Insufficiency Cohort Study G (2009) Chronic renal insufficiency cohort (CRIC) study: baseline characteristics and associations with kidney function. Clin J Am Soc Nephrol 4:1302–1311

    Article  PubMed  PubMed Central  Google Scholar 

  48. Brezis M, Greenfeld Z, Shina A, Rosen S (1990) Angiotensin II augments medullary hypoxia and predisposes to acute renal failure. Eur J Clin Invest 20:199–207

    Article  CAS  PubMed  Google Scholar 

  49. Bader M, Peters J, Baltatu O, Muller DN, Luft FC, Ganten D (2001) Tissue renin-angiotensin systems: new insights from experimental animal models in hypertension research. J Mol Med (Berl) 79:76–102

    Article  CAS  Google Scholar 

  50. Friederich-Persson M, Thorn E, Hansell P, Nangaku M, Levin M, Palm F (2013) Kidney hypoxia, attributable to increased oxygen consumption, induces nephropathy independently of hyperglycemia and oxidative stress. Hypertension 62:914–919

    Article  CAS  PubMed  Google Scholar 

  51. Hansell P, Welch WJ, Blantz RC, Palm F (2013) Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension. Clin Exp Pharmacol Physiol 40:123–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Welch WJ, Baumgartl H, Lubbers D, Wilcox CS (2003) Renal oxygenation defects in the spontaneously hypertensive rat: role of AT1 receptors. Kidney Int 63:202–208

    Article  CAS  PubMed  Google Scholar 

  53. Fu Q, Colgan SP, Shelley CS (2016) Hypoxia: the force that drives chronic kidney disease. Clin Med Res 14:15–39

    Article  PubMed  PubMed Central  Google Scholar 

  54. Fine LG, Bandyopadhay D, Norman JT (2000) Is there a common mechanism for the progression of different types of renal diseases other than proteinuria? Towards the unifying theme of chronic hypoxia. Kidney Int Suppl 75:S22–S26

    Article  CAS  PubMed  Google Scholar 

  55. Adler S, Huang H (2002) Impaired regulation of renal oxygen consumption in spontaneously hypertensive rats. J Am Soc Nephrol 13:1788–1794

    Article  CAS  PubMed  Google Scholar 

  56. Nistala R, Whaley-Connell A, Sowers JR (2008) Redox control of renal function and hypertension. Antioxid Redox Signal 10:2047–2089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Cowley AW Jr, Abe M, Mori T, O’Connor PM, Ohsaki Y, Zheleznova NN (2015) Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension. Am J Physiol Renal Physiol 308:F179–F197

    Article  CAS  PubMed  Google Scholar 

  58. Beltowski J (2010) Hypoxia in the renal medulla: implications for hydrogen sulfide signaling. J Pharmacol Exp Ther 334:358–363

    Article  CAS  PubMed  Google Scholar 

  59. Taylor NE, Cowley AW Jr (2005) Effect of renal medullary H2O2 on salt-induced hypertension and renal injury. Am J Physiol Regul Integr Comp Physiol 289:R1573–R1579

    Article  CAS  PubMed  Google Scholar 

  60. Pelisse JM (1969) Giant mitochondria in proximal tubule cells of diseased human kidney. Presse Med 77:1860

    CAS  PubMed  Google Scholar 

  61. Forbes JM, Ke BX, Nguyen TV, Henstridge DC, Penfold SA, Laskowski A, Sourris KC, Groschner LN, Cooper ME, Thorburn DR, Coughlan MT (2013) Deficiency in mitochondrial complex I activity due to Ndufs6 gene trap insertion induces renal disease. Antioxid Redox Signal 19:331–343

    Article  CAS  PubMed  Google Scholar 

  62. Coughlan MT, Higgins GC, Nguyen TV, Penfold SA, Thallas-Bonke V, Tan SM, Ramm G, Van Bergen NJ, Henstridge DC, Sourris KC, Harcourt BE, Trounce IA, Robb PM, Laskowski A, McGee SL, Genders AJ, Walder K, Drew BG, Gregorevic P, Qian H, Thomas MC, Jerums G, Macisaac RJ, Skene A, Power DA, Ekinci EI, Wijeyeratne XW, Gallo LA, Herman-Edelstein M, Ryan MT, Cooper ME, Thorburn DR, Forbes JM (2016) Deficiency in apoptosis-inducing factor recapitulates chronic kidney disease via aberrant mitochondrial homeostasis. Diabetes 65:1085–1098

    Article  CAS  PubMed  Google Scholar 

  63. Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, Park AS, Tao J, Sharma K, Pullman J, Bottinger EP, Goldberg IJ, Susztak K (2015) Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med 21:37–46

    Article  CAS  PubMed  Google Scholar 

  64. Eirin A, Saad A, Tang H, Herrmann SM, Woollard JR, Lerman A, Textor SC, Lerman LO (2016) Urinary mitochondrial DNA copy number identifies chronic renal injury in hypertensive patients. Hypertension 68:401–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Eirin A, Ebrahimi B, Zhang X, Zhu XY, Woollard JR, He Q, Textor SC, Lerman A, Lerman LO (2014) Mitochondrial protection restores renal function in swine atherosclerotic renovascular disease. Cardiovasc Res 103:461–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Szeto HH, Liu S, Soong Y, Alam N, Prusky GT, Seshan SV (2016) Protection of mitochondria prevents high-fat diet-induced glomerulopathy and proximal tubular injury. Kidney Int 90:997–1011

    Article  CAS  PubMed  Google Scholar 

  67. Eirin A, Lerman A, Lerman LO (2016) The emerging role of mitochondrial targeting in kidney disease. Handb Exp Pharmacol. doi:10.1007/164_2016_6

    Google Scholar 

  68. Johnson JL, van Eys GJ, Angelini GD, George SJ (2001) Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein. Arterioscler Thromb Vasc Biol 21:1146–1151

    Article  CAS  PubMed  Google Scholar 

  69. Chalmers S, Saunter C, Wilson C, Coats P, Girkin JM, McCarron JG (2012) Mitochondrial motility and vascular smooth muscle proliferation. Arterioscler Thromb Vasc Biol 32:3000–3011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Marsboom G, Toth PT, Ryan JJ, Hong Z, Wu X, Fang YH, Thenappan T, Piao L, Zhang HJ, Pogoriler J, Chen Y, Morrow E, Weir EK, Rehman J, Archer SL (2012) Dynamin-related protein 1-mediated mitochondrial mitotic fission permits hyperproliferation of vascular smooth muscle cells and offers a novel therapeutic target in pulmonary hypertension. Circ Res 110:1484–1497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wang L, Yu T, Lee H, O’Brien DK, Sesaki H, Yoon Y (2015) Decreasing mitochondrial fission diminishes vascular smooth muscle cell migration and ameliorates intimal hyperplasia. Cardiovasc Res 106:272–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ryan J, Dasgupta A, Huston J, Chen KH, Archer SL (2015) Mitochondrial dynamics in pulmonary arterial hypertension. J Mol Med (Berl) 93:229–242

    Article  CAS  Google Scholar 

  73. Freund-Michel V, Khoyrattee N, Savineau JP, Muller B, Guibert C (2014) Mitochondria: roles in pulmonary hypertension. Int J Biochem Cell Biol 55:93–97

    Article  CAS  PubMed  Google Scholar 

  74. Zhang DX, Gutterman DD (2007) Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol 292:H2023–H2031

    Article  CAS  PubMed  Google Scholar 

  75. Scheitlin CG, Julian JA, Shanmughapriya S, Madesh M, Tsoukias NM, Alevriadou BR (2016) Endothelial mitochondria regulate the intracellular Ca2+ response to fluid shear stress. Am J Physiol Cell Physiol 310:C479–C490

    Article  PubMed  PubMed Central  Google Scholar 

  76. Dedkova EN, Ji X, Lipsius SL, Blatter LA (2004) Mitochondrial calcium uptake stimulates nitric oxide production in mitochondria of bovine vascular endothelial cells. Am J Physiol Cell Physiol 286:C406–C415

    Article  CAS  PubMed  Google Scholar 

  77. Li H, Liu Z, Gou Y, Yu H, Siminelakis S, Wang S, Kong D, Zhou Y, Liu Z, Ding Y, Yao D (2015) Estradiol mediates vasculoprotection via ERRalpha-dependent regulation of lipid and ROS metabolism in the endothelium. J Mol Cell Cardiol 87:92–101

    Article  CAS  PubMed  Google Scholar 

  78. Groschner LN, Waldeck-Weiermair M, Malli R, Graier WF (2012) Endothelial mitochondria—less respiration, more integration. Pflugers Arch 464:63–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Scheitlin CG, Nair DM, Crestanello JA, Zweier JL, Alevriadou BR (2014) Fluid mechanical forces and endothelial mitochondria: a bioengineering perspective. Cell Mol Bioeng 7:483–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Domigan CK, Warren CM, Antanesian V, Happel K, Ziyad S, Lee S, Krall A, Duan L, Torres-Collado AX, Castellani LW, Elashoff D, Christofk HR, van der Bliek AM, Potente M, Iruela-Arispe ML (2015) Autocrine VEGF maintains endothelial survival through regulation of metabolism and autophagy. J Cell Sci 128:2236–2248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Moro MA, Almeida A, Bolanos JP, Lizasoain I (2005) Mitochondrial respiratory chain and free radical generation in stroke. Free Radic Biol Med 39:1291–1304

    Article  CAS  PubMed  Google Scholar 

  82. Jin Z, Wu J, Yan LJ (2016) Chemical conditioning as an approach to ischemic stroke tolerance: mitochondria as the target. Int J Mol Sci 17:351

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Kislin M, Sword J, Fomitcheva IV, Croom D, Pryazhnikov E, Lihavainen E, Toptunov D, Rauvala H, Ribeiro AS, Khiroug L, Kirov SA (2017) Reversible disruption of neuronal mitochondria by ischemic and traumatic injury revealed by quantitative two-photon imaging in the neocortex of anesthetized mice. J Neurosci 37:333–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gibbs WS, Weber RA, Schnellmann RG, Adkins DL (2016) Disrupted mitochondrial genes and inflammation following stroke. Life Sci 166:139–148

    Article  CAS  PubMed  Google Scholar 

  85. Mattson MP, Gleichmann M, Cheng A (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60:748–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Raefsky SM, Mattson MP (2017) Adaptive responses of neuronal mitochondria to bioenergetic challenges: roles in neuroplasticity and disease resistance. Free Radic Biol Med 102:203–216

    Article  CAS  PubMed  Google Scholar 

  87. Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, Ji X, Lo EH (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535:551–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Bukeirat M, Sarkar SN, Hu H, Quintana DD, Simpkins JW, Ren X (2016) MiR-34a regulates blood-brain barrier permeability and mitochondrial function by targeting cytochrome c. J Cereb Blood Flow Metab 36:387–392

    Article  CAS  PubMed  Google Scholar 

  89. Doll DN, Hu H, Sun J, Lewis SE, Simpkins JW, Ren X (2015) Mitochondrial crisis in cerebrovascular endothelial cells opens the blood-brain barrier. Stroke 46:1681–1689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Manucha W, Ritchie B, Ferder L (2015) Hypertension and insulin resistance: implications of mitochondrial dysfunction. Curr Hypertens Rep 17:504

    Article  PubMed  CAS  Google Scholar 

  91. Camporez JP, Asrih M, Zhang D, Kahn M, Samuel VT, Jurczak MJ, Jornayvaz FR (2015) Hepatic insulin resistance and increased hepatic glucose production in mice lacking Fgf21. J Endocrinol 226:207–217

    Article  CAS  PubMed  Google Scholar 

  92. Sebastian D, Hernandez-Alvarez MI, Segales J, Sorianello E, Munoz JP, Sala D, Waget A, Liesa M, Paz JC, Gopalacharyulu P, Oresic M, Pich S, Burcelin R, Palacin M, Zorzano A (2012) Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci USA 109:5523–5528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Gerbitz KD, van den Ouweland JM, Maassen JA, Jaksch M (1995) Mitochondrial diabetes mellitus: a review. Biochim Biophys Acta 1271:253–260

    Article  PubMed  Google Scholar 

  94. Rovira-Llopis S, Banuls C, Diaz-Morales N, Hernandez-Mijares A, Rocha M, Victor VM (2017) Mitochondrial dynamics in type 2 diabetes: pathophysiological implications. Redox Biol 11:637–645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Wilson-Fritch L, Nicoloro S, Chouinard M, Lazar MA, Chui PC, Leszyk J, Straubhaar J, Czech MP, Corvera S (2004) Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 114:1281–1289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Quiros PM, Ramsay AJ, Sala D, Fernandez-Vizarra E, Rodriguez F, Peinado JR, Fernandez-Garcia MS, Vega JA, Enriquez JA, Zorzano A, Lopez-Otin C (2012) Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice. EMBO J 31:2117–2133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Dietrich MO, Liu ZW, Horvath TL (2013) Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity. Cell 155:188–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Schneeberger M, Dietrich MO, Sebastian D, Imbernon M, Castano C, Garcia A, Esteban Y, Gonzalez-Franquesa A, Rodriguez IC, Bortolozzi A, Garcia-Roves PM, Gomis R, Nogueiras R, Horvath TL, Zorzano A, Claret M (2013) Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance. Cell 155:172–187

    Article  CAS  PubMed  Google Scholar 

  99. Maurizi CP (1995) The mystery of Alzheimer’s disease and its prevention by melatonin. Med Hypotheses 45:339–340

    Article  CAS  PubMed  Google Scholar 

  100. Okatani Y, Wakatsuki A, Reiter RJ, Miyahara Y (2002) Hepatic mitochondrial dysfunction in senescence-accelerated mice: correction by long-term, orally administered physiological levels of melatonin. J Pineal Res 33:127–133

    Article  CAS  PubMed  Google Scholar 

  101. Okatani Y, Wakatsuki A, Reiter RJ, Miyahara Y (2003) Acutely administered melatonin restores hepatic mitochondrial physiology in old mice. Int J Biochem Cell Biol 35:367–375

    Article  CAS  PubMed  Google Scholar 

  102. Reiter RJ, Guerrero JM, Garcia JJ, Acuna-Castroviejo D (1998) Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin. Ann N Y Acad Sci 854:410–424

    Article  CAS  PubMed  Google Scholar 

  103. Stacchiotti A, Lavazza A, Rezzani R, Bianchi R (2002) Cyclosporine A-induced kidney alterations are limited by melatonin in rats: an electron microscope study. Ultrastruct Pathol 26:81–87

    Article  CAS  PubMed  Google Scholar 

  104. Balli E, Mete UO, Tuli A, Tap O, Kaya M (2004) Effect of melatonin on the cardiotoxicity of doxorubicin. Histol Histopathol 19:1101–1108

    CAS  PubMed  Google Scholar 

  105. Esrefoglu M, Gul M, Ates B, Erdogan A (2011) The effects of caffeic acid phenethyl ester and melatonin on age-related vascular remodeling and cardiac damage. Fundam Clin Pharmacol 25:580–590

    Article  CAS  PubMed  Google Scholar 

  106. Rodriguez MI, Carretero M, Escames G, Lopez LC, Maldonado MD, Tan DX, Reiter RJ, Acuna-Castroviejo D (2007) Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice. Free Radic Res 41:15–24

    Article  CAS  PubMed  Google Scholar 

  107. Petrosillo G, Di Venosa N, Pistolese M, Casanova G, Tiravanti E, Colantuono G, Federici A, Paradies G, Ruggiero FM (2006) Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia-reperfusion: role of cardiolipin. FASEB J 20:269–276

    Article  CAS  PubMed  Google Scholar 

  108. Petrosillo G, Di Venosa N, Moro N, Colantuono G, Paradies V, Tiravanti E, Federici A, Ruggiero FM, Paradies G (2011) In vivo hyperoxic preconditioning protects against rat-heart ischemia/reperfusion injury by inhibiting mitochondrial permeability transition pore opening and cytochrome c release. Free Radic Biol Med 50:477–483

    Article  CAS  PubMed  Google Scholar 

  109. Petrosillo G, Colantuono G, Moro N, Ruggiero FM, Tiravanti E, Di Venosa N, Fiore T, Paradies G (2009) Melatonin protects against heart ischemia-reperfusion injury by inhibiting mitochondrial permeability transition pore opening. Am J Physiol Heart Circ Physiol 297:H1487–H1493

    Article  CAS  PubMed  Google Scholar 

  110. Mukherjee D, Ghosh AK, Bandyopadhyay A, Basu A, Datta S, Pattari SK, Reiter RJ, Bandyopadhyay D (2012) Melatonin protects against isoproterenol-induced alterations in cardiac mitochondrial energy-metabolizing enzymes, apoptotic proteins, and assists in complete recovery from myocardial injury in rats. J Pineal Res 53:166–179

    Article  CAS  PubMed  Google Scholar 

  111. Winiarska K, Drozak J, Wegrzynowicz M, Fraczyk T, Bryla J (2004) Diabetes-induced changes in glucose synthesis, intracellular glutathione status and hydroxyl free radical generation in rabbit kidney-cortex tubules. Mol Cell Biochem 261:91–98

    Article  CAS  PubMed  Google Scholar 

  112. Zavodnik IB, Lapshina EA, Cheshchevik VT, Dremza IK, Kujawa J, Zabrodskaya SV, Reiter RJ (2011) Melatonin and succinate reduce rat liver mitochondrial dysfunction in diabetes. J Physiol Pharmacol 62:421–427

    CAS  PubMed  Google Scholar 

  113. Teodoro BG, Baraldi FG, Sampaio IH, Bomfim LH, Queiroz AL, Passos MA, Carneiro EM, Alberici LC, Gomis R, Amaral FG, Cipolla-Neto J, Araujo MB, Lima T, Akira Uyemura S, Silveira LR, Vieira E (2014) Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle. J Pineal Res 57:155–167

    Article  CAS  PubMed  Google Scholar 

  114. Jimenez-Aranda A, Fernandez-Vazquez G, Campos D, Tassi M, Velasco-Perez L, Tan DX, Reiter RJ, Agil A (2013) Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats. J Pineal Res 55:416–423

    CAS  PubMed  Google Scholar 

  115. Jimenez-Aranda A, Fernandez-Vazquez G, Mohammad ASM, Reiter RJ, Agil A (2014) Melatonin improves mitochondrial function in inguinal white adipose tissue of Zucker diabetic fatty rats. J Pineal Res 57:103–109

    Article  CAS  PubMed  Google Scholar 

  116. Leon J, Acuna-Castroviejo D, Escames G, Tan DX, Reiter RJ (2005) Melatonin mitigates mitochondrial malfunction. J Pineal Res 38:1–9

    Article  CAS  PubMed  Google Scholar 

  117. Paradies G, Paradies V, Ruggiero FM, Petrosillo G (2015) Protective role of melatonin in mitochondrial dysfunction and related disorders. Arch Toxicol 89:923–939

    Article  CAS  PubMed  Google Scholar 

  118. Nemer M, Dali-Youcef N, Wang H, Aries A, Paradis P (2006) Mechanisms of angiotensin II-dependent progression to heart failure. Novartis Found Symp 274:58–68 (discussion 68–72, 152–155, 272–156)

    Article  CAS  PubMed  Google Scholar 

  119. Hamilton DJ, Zhang A, Li S, Cao TN, Smith JA, Vedula I, Cordero-Reyes AM, Youker KA, Torre-Amione G, Gupte AA (2016) Combination of angiotensin II and l-NG-nitroarginine methyl ester exacerbates mitochondrial dysfunction and oxidative stress to cause heart failure. Am J Physiol Heart Circ Physiol 310:H667–H680

    Article  PubMed  Google Scholar 

  120. Hernandez JS, Barreto-Torres G, Kuznetsov AV, Khuchua Z, Javadov S (2014) Crosstalk between AMPK activation and angiotensin II-induced hypertrophy in cardiomyocytes: the role of mitochondria. J Cell Mol Med 18:709–720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Chaplin NL, Nieves-Cintron M, Fresquez AM, Navedo MF, Amberg GC (2015) Arterial smooth muscle mitochondria amplify hydrogen peroxide microdomains functionally coupled to L-type calcium channels. Circ Res 117:1013–1023

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Lu Y, Li S, Wu H, Bian Z, Xu J, Gu C, Chen X, Yang D (2015) Beneficial effects of astragaloside IV against angiotensin II-induced mitochondrial dysfunction in rat vascular smooth muscle cells. Int J Mol Med 36:1223–1232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Choi H, Tostes RC, Webb RC (2011) Mitochondrial aldehyde dehydrogenase prevents ROS-induced vascular contraction in angiotensin-II hypertensive mice. J Am Soc Hypertens 5:154–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. De Cavanagh EM, Toblli JE, Ferder L, Piotrkowski B, Stella I, Fraga CG, Inserra F (2005) Angiotensin II blockade improves mitochondrial function in spontaneously hypertensive rats. Cell Mol Biol (Noisy-le-grand) 51:573–578

    Google Scholar 

  125. de Cavanagh EM, Piotrkowski B, Basso N, Stella I, Inserra F, Ferder L, Fraga CG (2003) Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. FASEB J 17:1096–1098

    PubMed  Google Scholar 

  126. Sun L, Xiao L, Nie J, Liu FY, Ling GH, Zhu XJ, Tang WB, Chen WC, Xia YC, Zhan M, Ma MM, Peng YM, Liu H, Liu YH, Kanwar YS (2010) p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway. Am J Physiol Renal Physiol 299:F1014–F1025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Du J, Leng J, Zhang L, Bai G, Yang D, Lin H, Qin J (2016) Angiotensin II-induced apoptosis of human umbilical vein endothelial cells was inhibited by blueberry anthocyanin through bax- and caspase 3-dependent pathways. Med Sci Monit 22:3223–3228

    Article  PubMed  PubMed Central  Google Scholar 

  128. Doughan AK, Harrison DG, Dikalov SI (2008) Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res 102:488–496

    Article  CAS  PubMed  Google Scholar 

  129. Dikalov SI, Nazarewicz RR (2013) Angiotensin II-induced production of mitochondrial reactive oxygen species: potential mechanisms and relevance for cardiovascular disease. Antioxid Redox Signal 19:1085–1094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ji ZZ, Xu YC (2016) Melatonin protects podocytes from angiotensin II-induced injury in an in vitro diabetic nephropathy model. Mol Med Rep 14(1):920–926. doi:10.3892/mmr.2016.5313

    Article  CAS  PubMed  Google Scholar 

  131. Ogawa S, Kobori H, Ohashi N, Urushihara M, Nishiyama A, Mori T, Ishizuka T, Nako K, Ito S (2009) Angiotensin II type 1 receptor blockers reduce urinary angiotensinogen excretion and the levels of urinary markers of oxidative stress and inflammation in patients with type 2 diabetic nephropathy. Biomark Insights 4:97–102

    CAS  PubMed  PubMed Central  Google Scholar 

  132. de Alencar Franco Costa D, Todiras M, Campos LA, Cipolla-Neto J, Bader M, Baltatu OC (2015) Sex-dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy. Acta Physiol (Oxf) 213:740–746

    Article  CAS  Google Scholar 

  133. Grois L, Hupf J, Reinders J, Schroder J, Dietl A, Schmid PM, Jungbauer C, Resch M, Maier LS, Luchner A, Birner C (2017) Combined inhibition of the renin-angiotensin system and neprilysin positively influences complex mitochondrial adaptations in progressive experimental heart failure. PLoS One 12:e0169743

    Article  PubMed  PubMed Central  Google Scholar 

  134. McLachlan J, Beattie E, Murphy MP, Koh-Tan CH, Olson E, Beattie W, Dominiczak AF, Nicklin SA, Graham D (2014) Combined therapeutic benefit of mitochondria-targeted antioxidant, MitoQ10, and angiotensin receptor blocker, losartan, on cardiovascular function. J Hypertens 32:555–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Manella G, Asher G (2016) The circadian nature of mitochondrial biology. Front Endocrinol (Lausanne) 7:162

    Google Scholar 

  136. Simon N, Papa K, Vidal J, Boulamery A, Bruguerolle B (2003) Circadian rhythms of oxidative phosphorylation: effects of rotenone and melatonin on isolated rat brain mitochondria. Chronobiol Int 20:451–461

    Article  CAS  PubMed  Google Scholar 

  137. Sarti P, Magnifico MC, Altieri F, Mastronicola D, Arese M (2013) New evidence for cross talk between melatonin and mitochondria mediated by a circadian-compatible interaction with nitric oxide. Int J Mol Sci 14:11259–11276

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Campos LA, Plehm R, Cipolla-Neto J, Bader M, Baltatu OC (2006) Altered circadian rhythm reentrainment to light phase shifts in rats with low levels of brain angiotensinogen. Am J Physiol Regul Integr Comp Physiol 290:R1122–R1127

    Article  CAS  PubMed  Google Scholar 

  139. Baltatu O, Janssen BJ, Bricca G, Plehm R, Monti J, Ganten D, Bader M (2001) Alterations in blood pressure and heart rate variability in transgenic rats with low brain angiotensinogen. Hypertension 37:408–413

    Article  CAS  PubMed  Google Scholar 

  140. Andersen LP, Gogenur I, Rosenberg J, Reiter RJ (2016) The safety of melatonin in humans. Clin Drug Investig 36:169–175

    Article  CAS  PubMed  Google Scholar 

  141. Galley HF, Lowes DA, Allen L, Cameron G, Aucott LS, Webster NR (2014) Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis. J Pineal Res 56:427–438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Grossman E, Laudon M, Yalcin R, Zengil H, Peleg E, Sharabi Y, Kamari Y, Shen-Orr Z, Zisapel N (2006) Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med 119:898–902

    Article  CAS  PubMed  Google Scholar 

  143. Cavallo A, Daniels SR, Dolan LM, Khoury JC, Bean JA (2004) Blood pressure response to melatonin in type 1 diabetes. Pediatr Diabetes 5:26–31

    Article  PubMed  Google Scholar 

  144. Goyal A, Terry PD, Superak HM, Nell-Dybdahl CL, Chowdhury R, Phillips LS, Kutner MH (2014) Melatonin supplementation to treat the metabolic syndrome: a randomized controlled trial. Diabetol Metab Syndr 6:124

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Tamura H, Nakamura Y, Narimatsu A, Yamagata Y, Takasaki A, Reiter RJ, Sugino N (2008) Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levels. J Pineal Res 45:101–105

    Article  CAS  PubMed  Google Scholar 

  146. Wakatsuki A, Okatani Y, Ikenoue N, Izumiya C, Kaneda C (2000) Melatonin inhibits oxidative modification of low-density lipoprotein particles in normolipidemic post-menopausal women. J Pineal Res 28:136–142

    Article  CAS  PubMed  Google Scholar 

  147. Pawlikowski M, Kolomecka M, Wojtczak A, Karasek M (2002) Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women. Neuro Endocrinol Lett 23(Suppl 1):17–19

    CAS  PubMed  Google Scholar 

  148. Rindone JP, Achacoso R (1997) Effect of melatonin on serum lipids in patients with hypercholesterolemia: a pilot study. Am J Ther 4:409–411

    Article  CAS  PubMed  Google Scholar 

  149. Cagnacci A, Arangino S, Renzi A, Paoletti AM, Melis GB, Cagnacci P, Volpe A (2001) Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf) 54:339–346

    Article  CAS  Google Scholar 

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Acknowledgements

FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) grant 2014/50457-0 to JCN. Cnpq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) Grant 446888/2014-1 to FGA.

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Baltatu, O.C., Amaral, F.G., Campos, L.A. et al. Melatonin, mitochondria and hypertension. Cell. Mol. Life Sci. 74, 3955–3964 (2017). https://doi.org/10.1007/s00018-017-2613-y

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