Advertisement

Anti-Inflammatory Effects of Melatonin in Obesity and Hypertension

  • Natalia Jorgelina Prado
  • León Ferder
  • Walter Manucha
  • Emiliano Raúl DiezEmail author
Hypertension and Obesity (E Reisin, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Hypertension and Obesity

Abstract

Purpose of Review

Here, we review the known relations between hypertension and obesity to inflammation and postulate the endogenous protective effect of melatonin and its potential as a therapeutic agent. We will describe the multiple effects of melatonin on blood pressure, adiposity, body weight, and focus on mitochondrial-related anti-inflammatory and antioxidant protective effects.

Recent Findings

Hypertension and obesity are usually associated with systemic and tissular inflammation. The progressive affection of target-organs involves multiple mediators of inflammation, most of them redundant, which make anti-inflammatory strategies ineffective. Melatonin reduces blood pressure, body weight, and inflammation. The mechanisms of action of this ancient molecule of protection involve multiple levels of action, from subcellular to intercellular. Mitochondria is a key inflammatory element in vascular and adipose tissue and a potential pharmacological target. Melatonin protects against mitochondrial dysfunction.

Summary

Melatonin reduces blood pressure and adipose tissue dysfunction by multiple anti-inflammatory/antioxidant actions and provides potent protection against mitochondria-mediated injury in hypertension and obesity. This inexpensive and multitarget molecule has great therapeutic potential against both epidemic diseases.

Keywords

Melatonin Hypertension Obesity Inflammation Oxidative stress Mitochondria 

Notes

Authors’ Contributions

All authors contributed to the manuscript writing. The authors have read and approved the final version of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

Natalia Prado, León Ferder, Walter Manucha, and Emiliano Diez declare no conflicts of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    •• Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults. J Am Coll Cardiol. 2017;S0735–663 1097(17)41519–1.  https://doi.org/10.1016/j.jacc.2017.11.006. Despite controversial, the new guidelines underlie the need to increase prevention. 10.1016/j.jacc.2017.11.006.
  2. 2.
    Carretero OA, Oparil S. Essential hypertension. Part I: definition and etiology. Circulation. 2000;101(3):329–3325.Google Scholar
  3. 3.
    Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden Of Disease Study 2013. Lancet. 2014;384(9945):766–81.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Jih J, Mukherjea A, Vittinghoff E, Nguyen TT, Tsoh JY, Fukuoka Y, et al. Using appropriate body mass index cut points for overweight and obesity among Asian Americans. Prev Med (Baltim). 2014;65:1–6.CrossRefGoogle Scholar
  5. 5.
    Guida B, Cataldi M, Maresca ID, Germanò R, Trio R, Nastasi AM. Dietary intake as a link between obesity, systemic inflammation, and the assumption of multiple cardiovascular and antidiabetic drugs in renal transplant recipients. Biomed Res Int. 2013;2013:1–8.CrossRefGoogle Scholar
  6. 6.
    •• Caillon A, Schiffrin EL. Role of inflammation and immunity in hypertension: recent epidemiological, laboratory, and clinical evidence. Curr Hypertens Rep. 2016;18(3):21. A deep review of systemic and local inflammatory responses in hypertension. Cellular and humoral interactions in almost every physiological system that contribute to hypertension pathophysiology. PubMedCrossRefGoogle Scholar
  7. 7.
    Bluher M. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance? Clin Sci. 2016;130(18):1603–14.PubMedCrossRefGoogle Scholar
  8. 8.
    Renna NF, Lembo C, Diez E, Miatello RM. Role of renin-angiotensin system and oxidative stress on vascular inflammation in insulin resistence model. Int J Hypertens. 2013;2013:420979.  https://doi.org/10.1155/2013/420979.
  9. 9.
    Renna NF, Diez ER, Lembo C, Miatello RM. Role of Cox-2 in vascular inflammation: an experimental model of metabolic syndrome. Mediat Inflamm. 2013;2013:1–10.CrossRefGoogle Scholar
  10. 10.
    •• Dorresteijn JAN, Visseren FLJ, Spiering W. Mechanisms linking obesity to hypertension. Obes Rev. 2012;13(1):17–26. This article describes the paracrine regulation of vascular response by mutual interactions between the endothelium, smooth muscle, and perivascular adipose tissue. PubMedCrossRefGoogle Scholar
  11. 11.
    Stolarczyk E. Adipose tissue inflammation in obesity: a metabolic or immune response? Curr Opin Pharmacol. 2017;37:35–40.PubMedCrossRefGoogle Scholar
  12. 12.
    Nava E, Llorens S. The paracrine control of vascular motion. A historical perspective. Pharmacol Res. 2016;113:125–45.PubMedCrossRefGoogle Scholar
  13. 13.
    •• Vazquez-Prieto MA, Renna NF, Diez ER, Cacciamani V, Lembo C, Miatello RM. Effect of red wine on adipocytokine expression and vascular alterations in fructose-fed rats. Am J Hypertens. 2011;24(2):234–40.  https://doi.org/10.1038/ajh.2010.214. This previous review from our group extensively covers the central role of mitochondrial dysfunction in feeding behavior, energy balance, autonomic response, oxidative stress, and inflammation.
  14. 14.
    Huby A-C, Antonova G, Groenendyk J, Gomez-Sanchez CE, Bollag WB, Filosa JA, et al. Adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis. Circulation. 2015;132(22):2134–45.PubMedCrossRefGoogle Scholar
  15. 15.
    Lahera V, de las Heras N, López-Farré A, Manucha W, Ferder L. Role of mitochondrial dysfunction in hypertension and obesity. Curr Hypertens Rep. 2017;19(2):11.PubMedCrossRefGoogle Scholar
  16. 16.
    Manfredi A, Rovere-Querini P. The mitochondrion—a Trojan horse that kicks off inflammation? N Engl J Med. 2010;362(22):2132–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Meyer JN, Leuthner TC, Luz AL. Mitochondrial fusion, fission, and mitochondrial toxicity. Toxicology. 2017;1(391)42–53.  https://doi.org/10.1016/j.tox.2017.07.019.
  18. 18.
    Ohashi N, Isobe S, Ishigaki S, Yasuda H. Circadian rhythm of blood pressure and the renin–angiotensin system in the kidney. Hypertens Res. 2017;40(5):413–22.PubMedCrossRefGoogle Scholar
  19. 19.
    Laermans J, Depoortere I. Chronobesity: role of the circadian system in the obesity epidemic. Obes Rev. 2016;17(2):108–25.PubMedCrossRefGoogle Scholar
  20. 20.
    • Reiter RJ, Rosales-Corral S, Tan DX, Jou MJ, Galano A, Xu B. Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Cell Mol Life Sci. 2017;74(21):3863–3881.  https://doi.org/10.1007/s00018-017-2609-7. This review covers most of the antioxidant mechanisms of melatonin with special attention to those relative to mitochondria.
  21. 21.
    Suofu Y, Li W, Jean-Alphonse FG, Jia J, Khattar NK, Li J, et al. Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release. Proc Natl Acad Sci U S A. 2017;114(38):E7997–8006.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    • Sharafati-Chaleshtori R, Shirzad H, Rafieian-Kopaei M, Soltani A. Melatonin and human mitochondrial diseases. J Res Med Sci. 2017;22:2. The mitochondrial pathological mechanisms and interactions with melatonin are covered by this review. PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Volt H, García JA, Doerrier C, Díaz-Casado ME, Guerra-Librero A, López LC, et al. Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin. J Pineal Res. 2016;60(2):193–205.PubMedCrossRefGoogle Scholar
  24. 24.
    •• Lüscher TF. Hypertension: detection, mechanisms, outcomes, and treatment. Eur Heart J. 2017;38(2):67–9. It is a well-illustrated review of hypertension. It addresses risk factor, pathogenic mechanisms, treatments, morbidity, and mortality. PubMedCrossRefGoogle Scholar
  25. 25.
    Marco VG, Aroor AR, Sowers JR. The pathophysiology of hypertension in patients with obesity. Nat Rev Endocrinol 2014;10(6):364–76.  https://doi.org/10.1038/nrendo.2014.44.
  26. 26.
    Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, et al. Hypertension. Nat Rev Dis Prim. 2018;4:18014.PubMedCrossRefGoogle Scholar
  27. 27.
    Schiffrin EL. Inflammation, immunity and development of essential hypertension. J Hypertens. 2014;32(2):228–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Coffman TM. Under pressure: the search for the essential mechanisms of hypertension. Nat Med. 2011;17(11):1402–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Ferdinand KC, Nasser SA. Management of Essential Hypertension. Cardiol Clin. 2017 May;35(2):231–46.PubMedCrossRefGoogle Scholar
  30. 30.
    Lee RM, Dickhout JG, Sandow SL. Vascular structural and functional changes: their association with causality in hypertension: models, remodeling and relevance. Hypertens Res. 2017;40(4):311–23.PubMedCrossRefGoogle Scholar
  31. 31.
    Simko F, Pechanova O. Remodelling of the heart and vessels in experimental hypertension: advances in protection. J Hypertens 2010;28 Suppl 1:S1–6.  https://doi.org/10.1097/01.hjh.0000388487.43460.db.
  32. 32.
    Renna NF, Diez EA, Miatello RM. Effects of dipeptidyl-peptidase 4 inhibitor about vascular inflammation in a metabolic syndrome model. PLoS One. 2014;9(9):e106563.  https://doi.org/10.1371/journal.pone.0106563.
  33. 33.
    Okuda T, Grollman A. Passive transfer of autoimmune induced hypertension in the rat by lymph node cells. Tex Rep Biol Med. 1967;25(2):257–64.PubMedGoogle Scholar
  34. 34.
    Norlander AE, Madhur MS, Harrison DG. The immunology of hypertension. J Exp Med. 2018;215(1):21–33.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Münzel T, Camici GG, Maack C, Bonetti NR, Fuster V, Kovacic JC. Impact of oxidative stress on the heart and vasculature: part 2 of a 3-part series. J Am Coll Cardiol. 2017;70(2):212–29.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Kalupahana NS, Moustaid-Moussa N. The renin-angiotensin system: a link between obesity, inflammation and insulin resistance. Obes Rev. 2012;13:136–49.PubMedCrossRefGoogle Scholar
  37. 37.
    D’Agati VD, Chagnac A, Vries AP, Levi M, Porrini E, Herman-Edelstein M. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat Rev Nephrol. 2016;12(8):453–71.  https://doi.org/10.1038/nrneph.2016.75.
  38. 38.
    Xia N, Li H. The role of perivascular adipose tissue in obesity-induced vascular dysfunction. Br J Pharmacol. 2017;174(20):3425–42.PubMedCrossRefGoogle Scholar
  39. 39.
    Imperatore R, Palomba L, Cristino L. Role of orexin-a in hypertension and obesity. Curr Hypertens Rep. 2017;19(4):34.PubMedCrossRefGoogle Scholar
  40. 40.
    Ingaramo RA. Obesity, diabetes, and other cardiovascular risk factors in native populations of South America. Curr Hypertens Rep. 2016;18(1):9.PubMedCrossRefGoogle Scholar
  41. 41.
    Soltani S, Shirani F, Chitsazi MJ, Salehi-Abargouei A. The effect of dietary approaches to stop hypertension (DASH) diet on weight and body composition in adults: a systematic review and meta-analysis of randomized controlled clinical trials. Obes Rev. 2016;17(5):442–54.PubMedCrossRefGoogle Scholar
  42. 42.
    Scholz GH, Hanefeld M. Metabolic vascular syndrome: new insights into a multidimensional network of risk factors and diseases. Visc Med. 2016;32(5):319–26.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Kannel WB, Brand N, Skinner JJ, Dawber TR, McNamara PM. The relation of adiposity to blood pressure and development of hypertension. The Framingham study Ann Intern Med. 1967;67(1):48–59.PubMedCrossRefGoogle Scholar
  44. 44.
    Bramlage P, Pittrow D, Wittchen HU, Kirch W, Boehler S, Lehnert H. Hypertension in overweight and obese primary care patients is highly prevalent and poorly controlled. Am J Hypertens. 2004;17:904–10.PubMedCrossRefGoogle Scholar
  45. 45.
    Canning KL, Brown RE, Wharton S, Sharma AM, Kuk JL. Edmonton obesity staging system prevalence and association with weight loss in a publicly funded referral-based obesity clinic. J Obes. 2015;2015:1–7.CrossRefGoogle Scholar
  46. 46.
    Hales CM, Carroll MD, Simon PA, Kuo T, Ogden CL. Hypertension prevalence, awareness, treatment, and control among adults aged ≥18 years—Los Angeles County, 1999-2006 and 2007-2014. MMWR Morb Mortal Wkly Rep. 2017;66(32):846–9.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Kotsis V, Nilsson P, Grassi G, Mancia G, Redon J, Luft F, et al. New developments in the pathogenesis of obesity-induced hypertension. J Hypertens. 2015;33(8):1499–508.PubMedCrossRefGoogle Scholar
  48. 48.
    Movahed MR, Lee JZ, Lim WY, Hashemzadeh M. Strong independent association between obesity and essential hypertension. Clin Obes. 2016;6(3):189–92.PubMedCrossRefGoogle Scholar
  49. 49.
    Ramirez JG, O’Malley EJ, Ho WSV. Pro-contractile effects of perivascular fat in health and disease. Br J Pharmacol. 2017;174(20):3482–95.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Niemann B, Rohrbach S, Miller MR, Newby DE, Fuster V, Kovacic JC. Oxidative stress and cardiovascular risk: obesity, diabetes, smoking, and pollution: part 3 of a 3-part series. J Am Coll Cardiol. 2017;70(2):230–51.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    do Carmo JM, da Silva AA, Wang Z, Fang T, Aberdein N, de Lara Rodriguez CEP, et al. Obesity-induced hypertension: brain signaling pathways. Curr Hypertens Rep. 2016;18(7):58.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Lim K, Jackson KL, Sata Y, Head GA. Factors responsible for obesity-related hypertension. Curr Hypertens Rep. 2017;19(7):53.PubMedCrossRefGoogle Scholar
  53. 53.
    Ramos-Romero S, Hereu M, Atienza L, Casas J, Jáuregui O, Amézqueta S, et al. Mechanistically different effects of fat and sugar on insulin resistance, hypertension and gut microbiota in rats. Am J Physiol Metab. 2018;  https://doi.org/10.1152/ajpendo.00323.2017.
  54. 54.
    Stafeev IS, Vorotnikov AV, Ratner EI, Menshikov MY, Parfyonova YV. Latent inflammation and insulin resistance in adipose tissue. Int J Endocrinol. 2017;2017:1–12.CrossRefGoogle Scholar
  55. 55.
    Mansukhani MP, Kara T, Caples SM, Somers VK. Chemoreflexes, sleep apnea, and sympathetic dysregulation. Curr Hypertens Rep. 2014 Sep;16(9):476.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Konecny T, Kara T, Somers VK. Obstructive sleep apnea and hypertension: an update. Hypertension. 2014;63(2):203–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Lohmeier TE, Iliescu R, Tudorancea I, Cazan R, Cates AW, Georgakopoulos D, et al. Chronic interactions between carotid baroreceptors and chemoreceptors in obesity hypertension. Hypertension. 2016;68(1):227–35.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Goodfriend TL, Ball DL, Egan BM, Campbell WB, Nithipatikom K. Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. Hypertension. 2004;43(2):358–63.PubMedCrossRefGoogle Scholar
  59. 59.
    Jeon JH, Kim K-Y, Kim JH, Baek A, Cho H, Lee YH, et al. A novel adipokine CTRP1 stimulates aldosterone production. FASEB J. 2007;22(5):1502–11.CrossRefGoogle Scholar
  60. 60.
    Bentley-Lewis R, Adler GK, Perlstein T, Seely EW, Hopkins PN, Williams GH, et al. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet. J Clin Endocrinol Metab. 2007;92(11):4472–5.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Lian X, Gollasch M. A clinical perspective: contribution of dysfunctional perivascular adipose tissue (PVAT) to cardiovascular risk. Curr Hypertens Rep. 2016;18(11):82.PubMedCrossRefGoogle Scholar
  62. 62.
    da Costa RM, Fais RS, Dechandt CRP, Louzada-Junior P, Alberici LC, Lobato NS, et al. Increased mitochondrial ROS generation mediates the loss of the anti-contractile effects of perivascular adipose tissue in high-fat diet obese mice. Br J Pharmacol. 2017;174(20):3527–41.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Jordan J, Nilsson PM, Kotsis V, Olsen MH, Grassi G, Yumuk V, et al. Joint scientific statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and early vascular ageing. J Hypertens. 2015;33(3):425–34.PubMedCrossRefGoogle Scholar
  64. 64.
    Owen JG, Reisin E. Anti-hypertensive drug treatment of patients with and the metabolic syndrome and obesity: a review of evidence, meta-analysis, post hoc and guidelines publications. Curr Hypertens Rep. 2015 Jun;17(6):558.PubMedCrossRefGoogle Scholar
  65. 65.
    Shah RV, Abbasi SA, Yamal J-M, Davis BR, Barzilay J, Einhorn PT, et al. Impaired fasting glucose and body mass index as determinants of mortality in ALLHAT: is the obesity paradox real? J Clin Hypertens. 2014;16(6):451–8.CrossRefGoogle Scholar
  66. 66.
    Siebenhofer A, Jeitler K, Horvath K, Berghold A, Siering U, Semlitsch T. Long-term effects of weight-reducing drugs in hypertensive patients. Cochrane Database Syst Rev. 2013;28(3):CD007654.  https://doi.org/10.1002/14651858.CD007654.pub3.
  67. 67.
    Sabaka P, Dukat A, Gajdosik J, Bendzala M, Caprnda M, Simko F. The effects of body weight loss and gain on arterial hypertension control: an observational prospective study. Eur J Med Res. 2017;22(1):43.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Seimon RV, Espinoza D, Ivers L, Gebski V, Finer N, Legler UF, et al. Changes in body weight and blood pressure: paradoxical outcome events in overweight and obese subjects with cardiovascular disease. Int J Obes. 2014;38(9):1165–71.CrossRefGoogle Scholar
  69. 69.
    Ndanuko RN, Tapsell LC, Charlton KE, Neale EP, Batterham MJ. Dietary patterns and blood pressure in adults: a systematic review and meta-analysis of randomized controlled trials. Adv Nutr. 2016;7(1):76–89.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Sorriento D, De Luca N, Trimarco B, Iaccarino G. The antioxidant therapy: new insights in the treatment of hypertension. Front Physiol. 2018;9:258.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Sjostrom CD, Peltonen M, Wedel H, Sjostrom L. Differential long-term effects of intentional weight loss on diabetes and hypertension. Hypertension. 2000;36(1):20–5.Google Scholar
  72. 72.
    Ho AK, Bartels CM, Thorpe CT, Pandhi N, Smith MA, Johnson HM. Achieving weight loss and hypertension control among obese adults: a US multidisciplinary group practice observational study. Am J Hypertens. 2016;29(8):984–91.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, et al. Association of pharmacological treatments for obesity with weight loss and adverse events. JAMA. 2016;315(22):2424–34.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and Management of Obesity. Longo DL, editor. N Engl J Med 2017;376(3):254–66.Google Scholar
  75. 75.
    Schiavon CA, Bersch-Ferreira AC, Santucci EV, Oliveira JD, Torreglosa CR, Bueno PT, et al. Effects of bariatric surgery in obese patients with hypertension: the GATEWAY Randomized Trial (gastric bypass to treat obese patients with steady hypertension). Circulation. 2018; 137(11):1132–1142.  https://doi.org/10.1161/CIRCULATIONAHA.117.032130.
  76. 76.
    Tan DX, Hardeland R, Manchester LC, Paredes SD, Korkmaz A, Sainz RM, et al. The changing biological roles of melatonin during evolution: from an antioxidant to signals of darkness, sexual selection and fitness. Biol Rev. 2010;85(3):607–23.PubMedGoogle Scholar
  77. 77.
    •• Pandi-Perumal SR, BaHammam AS, Ojike NI, Akinseye OA, Kendzerska T, Buttoo K, et al. Melatonin and human cardiovascular disease. J Cardiovasc Pharmacol Ther. 2017;22(2):122–32. Update information about melatonin cardiovascular effects. Clear information that supports melatonin potential as a therapeutic option. CrossRefPubMedGoogle Scholar
  78. 78.
    Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP, Olcese J. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev. 2010;62(3):343–80.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Jockers R, Maurice P, Boutin JA, Delagrange P. Melatonin receptors, heterodimerization, signal transduction and binding sites: what’s new? Br J Pharmacol. 2008;154(6):1182–95.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol. 2012;351(2):152–66.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Nosjean O, Nicolas JP, Klupsch F, Delagrange P, Canet E, Boutin JA. Comparative pharmacological studies of melatonin receptors: MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2. Biochem Pharmacol. 2001;61(11):1369–79.PubMedCrossRefGoogle Scholar
  82. 82.
    Emet M, Ozcan H, Ozel L, Yayla M, Halici Z, Hacimuftuoglu A. A review of melatonin, its receptors and drugs. Eurasian J Med. 2016;48(2):135–41.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Benítez-King G. Melatonin as a cytoskeletal modulator: implications for cell physiology and disease. J Pineal Res. 2006 Jan;40(1):1–9.PubMedCrossRefGoogle Scholar
  84. 84.
    •• Szewczyk-Golec K, Woźniak A, Reiter RJ. Inter-relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity. J Pineal Res. 2015:277–91. This revision describes the endocrine interaction between melatonin and adipokines in obesity. Chornobiology is relevant for obesity. Google Scholar
  85. 85.
    Tan D-X, Manchester LC, Terron MP, Flores LJ, Reiter RJ. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res. 2007;42(1):28–42.PubMedCrossRefGoogle Scholar
  86. 86.
    Dominguez-Rodriguez A, Abreu-Gonzalez P. Melatonin: still a forgotten antioxidant. Int J Cardiol. 2011;149(3):382.PubMedCrossRefGoogle Scholar
  87. 87.
    Poeggeler B, Reiter RJ, Tan D-X, Chen L-D, Manchester LC. Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis. J Pineal Res. 1993;14(4):151–68.PubMedCrossRefGoogle Scholar
  88. 88.
    •• Baltatu OC, Amaral FG, Campos LA, Cipolla-Neto J. Melatonin, mitochondria and hypertension. Cell Mol Life Sci. 2017;74(21):3955–64. This revision is of great relevance for the topic of the present review. It describes of the several mechanisms of action of melatonin on mitochondria and highlight those relevant to hypertension. PubMedCrossRefGoogle Scholar
  89. 89.
    Dwaich KH, Al-Amran FGY, Al-Sheibani BIM, Al-Aubaidy HA. Melatonin effects on myocardial ischemia-reperfusion injury: impact on the outcome in patients undergoing coronary artery bypass grafting surgery. Int J Cardiol. 2016;221:977–86.PubMedCrossRefGoogle Scholar
  90. 90.
    Diez ER, Renna NF, Prado NJ, Lembo C, Ponce Zumino AZ, Vazquez-Prieto M, et al. Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose-fed rats and spontaneously hypertensive rats. J Pineal Res. 2013;55(2):166–73.PubMedCrossRefGoogle Scholar
  91. 91.
    Russcher M, Koch B, Nagtegaal E, van der Putten K, ter Wee P, Gaillard C. The role of melatonin treatment in chronic kidney disease. Front Biosci (Landmark Ed). 2012;17:2644–56.CrossRefGoogle Scholar
  92. 92.
    Mauriz JL, Collado PS, Veneroso C, Reiter RJ, González-Gallego J. A review of the molecular aspects of melatonin’s anti-inflammatory actions: recent insights and new perspectives. J Pineal Res. 2013;54(1):1–14.PubMedCrossRefGoogle Scholar
  93. 93.
    García JA, Volt H, Venegas C, Doerrier C, Escames G, López LC, et al. Disruption of the NF-κB/NLRP3 connection by melatonin requires retinoid-related orphan receptor-α and blocks the septic response in mice. FASEB J. 2015;29(9):3863–75.PubMedCrossRefGoogle Scholar
  94. 94.
    Favero G, Franceschetti L, Bonomini F, Rodella LF, Rezzani R. Melatonin as an anti-inflammatory agent modulating Inflammasome activation. Int J Endocrinol. 2017;2017:1835195.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Touitou Y, Touitou D, Reinberg A. Disruption of adolescents’ circadian clock: the vicious circle of media use, exposure to light at night, sleep loss and risk behaviors. J Physiol. 2016;110(4):467–79.Google Scholar
  96. 96.
    Geiger SS, Fagundes CT, Siegel RM. Chrono-immunology: progress and challenges in understanding links between the circadian and immune systems. Immunology. 2015;146(3):349–58.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Yaprak M, Altun A, Vardar A, Aktoz M, Ciftci S, Ozbay G. Decreased nocturnal synthesis of melatonin in patients with coronary artery disease. Int J Cardiol. 2003;89(1):103–7.PubMedCrossRefGoogle Scholar
  98. 98.
    Xu W, Cai SY, Zhang Y, Wang Y, Ahammed GJ, Xia XJ, et al. Melatonin enhances thermotolerance by promoting cellular protein protection in tomato plants. J Pineal Res. 2016;61(4):457–69.PubMedCrossRefGoogle Scholar
  99. 99.
    Lemmer B. Signal transduction and chronopharmacology of regulation of circadian cardiovascular rhythms in animal models of human hypertension. Heart Fail Clin. 2017;13(4):739–57.PubMedCrossRefGoogle Scholar
  100. 100.
    Liu Z, Gan L, Xu Y, Luo D, Ren Q, Wu S, et al. Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue. J Pineal Res. 2017;63(1): e12414.  https://doi.org/10.1111/jpi.12414.
  101. 101.
    Antonelli M, Kushner I. It’s time to redefine inflammation. FASEB J. 2017;31(5):1787–91.PubMedCrossRefGoogle Scholar
  102. 102.
    Lanaspa MA, Kuwabara M, Andres-Hernando A, Li N, Cicerchi C, Jensen T, et al. High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism. Proc Natl Acad Sci. 2018;115(12):3138–43.PubMedCrossRefGoogle Scholar
  103. 103.
    Erren TC, Pape HG, Reiter RJ, Piekarski C. Chronodisruption and cancer. Naturwissenschaften. 2008;95(5):367–82.PubMedCrossRefGoogle Scholar
  104. 104.
    Erren TC, Grob JV. Civil time ≠ biological time: recent options for empirically testing possible effects of chronodisruption. Chronobiol Int. 2015;32(5):697–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Bonmati-Carrion MA, Arguelles-Prieto R, Martinez-Madrid MJ, Reiter R, Hardeland R, Rol MA, et al. Protecting the melatonin rhythm through circadian healthy light exposure. Int J Mol Sci. 2014 Dec 17;15(12):23448–500.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    De Farias TDSM, De Oliveira AC, Andreotti S, Do Amaral FG, Chimin P, De Proença ARA, et al. Pinealectomy interferes with the circadian clock genes expression in white adipose tissue. J Pineal Res. 2015;58(3):251–61.CrossRefGoogle Scholar
  107. 107.
    Brady TM. The role of obesity in the development of left ventricular hypertrophy among children and adolescents. Curr Hypertens Rep. 2016;18(1):3.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ Res. 2015;116(6):991–1006.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Kawarazaki W, Fujita T. The role of aldosterone in obesity-related hypertension. Am J Hypertens. 2016;29(4):415–23.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Zamora E, Lupón J, de Antonio M, Urrutia A, Coll R, Díez C, et al. The obesity paradox in heart failure: is etiology a key factor? Int J Cardiol. 2013;166(3):601–5.PubMedCrossRefGoogle Scholar
  111. 111.
    Ríos-Lugo MJ, Cano P, Jiménez-Ortega V, Fernández-Mateos MP, Scacchi PA, Cardinali DP, et al. Melatonin effect on plasma adiponectin, leptin, insulin, glucose, triglycerides and cholesterol in normal and high fat-fed rats. J Pineal Res. 2010;49(4):342–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Cardinali DP, Cano P, Jiménez-Ortega V, Esquifino AI. Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications. Neuroendocrinology. 2011;93(3):133–42.PubMedCrossRefGoogle Scholar
  113. 113.
    Jiménez-Aranda A, Fernández-Vázquez G, Campos D, Tassi M, Velasco-Perez L, Tan D-X, et al. Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats. J Pineal Res. 2013;55(4):416–23.  https://doi.org/10.1111/jpi.12089.
  114. 114.
    Reiter RJ, Tan DX, Korkmaz A, Ma S. Obesity and metabolic syndrome: association with chronodisruption, sleep deprivation, and melatonin suppression. Ann Med. 2012;44(6):564–77.PubMedCrossRefGoogle Scholar
  115. 115.
    Yang Y, Duan W, Jin Z, Yi W, Yan J, Zhang S, et al. JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury. J Pineal Res. 2013;55(3):275–86.PubMedCrossRefGoogle Scholar
  116. 116.
    Lim H-D, Kim Y-S, Ko S-H, Yoon I-J, Cho S-G, Chun Y-H, et al. Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway. J Pineal Res. 2012;53(3):225–37.PubMedCrossRefGoogle Scholar
  117. 117.
    Bartness TJ, Liu Y, Shrestha YB, Ryu V. Neural innervation of white adipose tissue and the control of lipolysis. Front Neuroendocrinol. 2014 Oct;35(4):473–93.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Patel SR, Hu FB. Short sleep duration and weight gain: a systematic review. Obesity (Silver Spring). 2008;16(3):643–53.CrossRefGoogle Scholar
  119. 119.
    Chaput JP. Is sleep deprivation a contributor to obesity in children? Eat Weight Disord. 2016 Mar;21(1):5–11.PubMedCrossRefGoogle Scholar
  120. 120.
    Markwald RR, Melanson EL, Smith MR, Higgins J, Perreault L, Eckel RH, et al. Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain. Proc Natl Acad Sci. 2013;110(14):5695–700.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Ganie SA, Dar TA, Bhat AH, Dar KB, Anees S, Zargar MA, et al. Melatonin: a potential anti-oxidant therapeutic agent for mitochondrial dysfunctions and related disorders. Rejuvenation Res. 2016;19(1):21–40.PubMedCrossRefGoogle Scholar
  122. 122.
    Wai T, Langer T. Mitochondrial dynamics and metabolic regulation. Trends Endocrinol Metab. 2016;27(2):105–17.PubMedCrossRefGoogle Scholar
  123. 123.
    Stacchiotti A, Favero G, Giugno L, Lavazza A, Reiter RJ, Rodella LF, et al. Mitochondrial and metabolic dysfunction in renal convoluted tubules of obese mice: protective role of melatonin. Ashton N, editor. PLoS One. 2014;9(10):e111141.Google Scholar
  124. 124.
    Carraro RS, Souza GF, Solon C, Razolli DS, Chausse B, Barbizan R, et al. Hypothalamic mitochondrial abnormalities occur downstream of inflammation in diet-induced obesity. Mol Cell Endocrinol. 2018;460:238–45.PubMedCrossRefGoogle Scholar
  125. 125.
    Dietrich MO, Liu Z-W, Horvath TL. Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity. Cell. 2013;155(1):188–99.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Baltatu O, Afeche SC. José dos Santos SH, Campos LA, Barbosa R, Michelini LC, et al. locally synthesized angiotensin modulates pineal melatonin generation. J Neurochem. 2002;80(2):328–34.PubMedCrossRefGoogle Scholar
  127. 127.
    Campos LA, Cipolla-Neto J, Amaral FG, Michelini LC, Bader M, Baltatu OC. The angiotensin-melatonin Axis. Int J Hypertens. 2013;2013:1–7.CrossRefGoogle Scholar
  128. 128.
    Vaidya A, Sun B, Larson C, Forman JP, Williams JS. Vitamin D3 therapy corrects the tissue sensitivity to angiotensin II akin to the action of a converting enzyme inhibitor in obese hypertensives: an interventional study. J Clin Endocrinol Metab. 2012;97(7):2456–65.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Ferder M, Inserra F, Manucha W, Ferder L. The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system. AJP Cell Physiol. 2013;304(11):C1027–39.CrossRefGoogle Scholar
  130. 130.
    García IM, Altamirano L, Mazzei L, Fornés M, Cuello-Carrión FD, Ferder L, et al. Vitamin D receptor-modulated Hsp70/AT1 expression may protect the kidneys of SHRs AT the structural and functional levels. Cell Stress Chaperones. 2014;19(4):479–91.PubMedCrossRefGoogle Scholar
  131. 131.
    Garcia IM, Altamirano L, Mazzei L, Fornes M, Molina MN, Ferder L, et al. Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy. AJP Ren Physiol. 2012;302(12):F1595–605.CrossRefGoogle Scholar
  132. 132.
    Calton EK, Keane KN, Soares MJ. The potential regulatory role of vitamin D in the bioenergetics of inflammation. Curr Opin Clin Nutr Metab Care. 2015;18(4):367–73.PubMedCrossRefGoogle Scholar
  133. 133.
    Haneklaus M, O’Neill LAJ. NLRP3 at the interface of metabolism and inflammation. Immunol Rev. 2015;265(1):53–62.PubMedCrossRefGoogle Scholar
  134. 134.
    Kim M-J, Yoon J-H, Ryu J-H. Mitophagy: a balance regulator of NLRP3 inflammasome activation. BMB Rep. 2016;49(10):529–35.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17(2):179–89.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Giordano A, Murano I, Mondini E, Perugini J, Smorlesi A, Severi I, et al. Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res. 2013;54(9):2423–36.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7(2):99–109.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Salminen A, Ojala J, Kaarniranta K, Kauppinen A. Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases. Cell Mol Life Sci. 2012;69(18):2999–3013.PubMedCrossRefGoogle Scholar
  139. 139.
    Whaley-Connell A, Sowers JR. Obesity and kidney disease: from population to basic science and the search for new therapeutic targets. Kidney Int. 2017 Aug;92(2):313–23.PubMedCrossRefGoogle Scholar
  140. 140.
    Ishigaki S, Ohashi N, Isobe S, Tsuji N, Iwakura T, Ono M, et al. Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease. Clin Exp Nephrol. 2016;20(6):878–84.PubMedCrossRefGoogle Scholar
  141. 141.
    Hussein MR, Ahmed OG, Hassan AF, Ahmed MA. Intake of melatonin is associated with amelioration of physiological changes, both metabolic and morphological pathologies associated with obesity: an animal model. Int J Exp Pathol. 2007;88(1):19–29.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Winiarska K, Focht D, Sierakowski B, Lewandowski K, Orlowska M, Usarek M. NADPH oxidase inhibitor, apocynin, improves renal glutathione status in Zucker diabetic fatty rats: a comparison with melatonin. Chem Biol Interact. 2014;218:12–9.PubMedCrossRefGoogle Scholar
  143. 143.
    Molina MN, Ferder LL, Manucha W. Emerging role of nitric oxide and heat shock proteins in insulin resistance. Curr Hypertens Rep. 2016;18(1):1–13.PubMedCrossRefGoogle Scholar
  144. 144.
    Sartori C, Dessen P, Mathieu C, Monney A, Bloch J, Nicod P, et al. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice. Endocrinology. 2009;150(12):5311–7.PubMedCrossRefGoogle Scholar
  145. 145.
    Motawi TK, Ahmed SA, AM Hamed, El-Maraghy SA, MW Aziz. Melatonin and/or rowatinex attenuate streptozotocin-induced diabetic renal injury in rats. J Biomed Res. 2017.  https://doi.org/10.7555/JBR.31.20160028.
  146. 146.
    Fujimoto E, Imai A, Utsuyama M, Sato K. Effects of in vitro heat shock on immune cells in diet-induced obese mice. J Therm Biol. 2017;69:124–31.PubMedCrossRefGoogle Scholar
  147. 147.
    Mazzei L, Docherty NG, Manucha W. Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy. Cell Stress Chaperones. 2015 Nov;20(6):893–906.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Fan ACY, Young JC. Function of cytosolic chaperones in Tom70-mediated mitochondrial import. Protein Pept Lett. 2011;18(2):122–31.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Santos JM, Kowluru RA. Impaired transport of mitochondrial transcription factor A (TFAM) and the metabolic memory phenomenon associated with the progression of diabetic retinopathy. Diabetes Metab Res Rev. 2013;29(3):204–13.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Wang Y, Katayama A, Terami T, Han X, Nunoue T, Zhang D, et al. Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes. Metabolism. 2015;64(6):677–88.PubMedCrossRefGoogle Scholar
  151. 151.
    Ding M, Ning J, Feng N, Li Z, Liu Z, Wang Y, et al. Dynamin-related protein 1-mediated mitochondrial fission contributes to post-traumatic cardiac dysfunction in rats and the protective effect of melatonin. J Pineal Res. 2018;64(1):e12447.  https://doi.org/10.1111/jpi.12447.
  152. 152.
    Hrenak J, Paulis L, Repova K, Aziriova S, Nagtegaal EJ, Reiter RJ, et al. Melatonin and renal protection: novel perspectives from animal experiments and human studies (review). Curr Pharm Des. 2015;21(7):936–49.PubMedCrossRefGoogle Scholar
  153. 153.
    Simko F. Chronobiology of blood pressure: emerging implications of melatonin. Eur J Clin Investig. 2012 Nov;42(11):1252–4.CrossRefGoogle Scholar
  154. 154.
    Zanoboni A, Zanoboni-Muciaccia W. Experimental hypertension in pinealectomized rats. Life Sci. 1967;6(21):2327–31.PubMedCrossRefGoogle Scholar
  155. 155.
    Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens Suppl. 2009 Aug;27(6):S17–20.PubMedCrossRefGoogle Scholar
  156. 156.
    Obayashi K, Saeki K, Iwamoto J, Okamoto N, Tomioka K, Nezu S, et al. Nocturnal urinary melatonin excretion is associated with non-dipper pattern in elderly hypertensives. Hypertens Res. 2013;36(8):736–40.PubMedCrossRefGoogle Scholar
  157. 157.
    Fabbian F, Smolensky MH, Tiseo R, Pala M, Manfredini R, Portaluppi F. Dipper and non-dipper blood pressure 24-hour patterns: circadian rhythm-dependent physiologic and pathophysiologic mechanisms. Chronobiol Int. 2013;30(1–2):17–30.PubMedCrossRefGoogle Scholar
  158. 158.
    Jonas M, Garfinkel D, Zisapel N, Laudon M, Grossman E. Impaired nocturnal melatonin secretion in non-dipper hypertensive patients. Blood Press. 2003;12(1):19–24.PubMedGoogle Scholar
  159. 159.
    Hermida RC, Ayala DE, Fernández JR, Mojón A, Crespo JJ, Ríos MT, et al. Bedtime blood pressure chronotherapy significantly improves hypertension management. Heart Fail Clin. 2017;13(4):759–73.PubMedCrossRefGoogle Scholar
  160. 160.
    Benova M, Herichova I, Stebelova K, Paulis L, Krajcirovicova K, Simko F, et al. Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats. Hypertens Res. 2009;32(4):242–7.PubMedCrossRefGoogle Scholar
  161. 161.
    Schepelmann M, Molcan L, Uhrova H, Zeman M, Ellinger I. The presence and localization of melatonin receptors in the rat aorta. Cell Mol Neurobiol. 2011;31(8):1257–65.PubMedCrossRefGoogle Scholar
  162. 162.
    Masana MI, Doolen S, Ersahin C, Al-Ghoul WM, Duckles SP, Dubocovich ML, et al. MT(2) melatonin receptors are present and functional in rat caudal artery. J Pharmacol Exp Ther. 2002;302(3):1295–302.PubMedCrossRefGoogle Scholar
  163. 163.
    Tunstall RR, Shukla P, Grazul-Bilska A, Sun C, O’Rourke ST. MT<inf>2</inf> receptors mediate the inhibitory effects of melatonin on nitric oxide-induced relaxation of porcine isolated coronary arteries. J Pharmacol Exp Ther. 2011;336(1):127-33.  https://doi.org/10.1124/jpet.110.174482.
  164. 164.
    Yang Q, Scalbert E, Delagrange P, Vanhoutte PM, O’Rourke ST. Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries. Am J Physiol Heart Circ Physiol. 2001;280(1):H76–82.PubMedCrossRefGoogle Scholar
  165. 165.
    Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJM, Zisapel N, et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol. 2008;85(3):335–53.PubMedCrossRefGoogle Scholar
  166. 166.
    Koziróg M, Poliwczak AR, Duchnowicz P, Koter-Michalak M, Sikora J, Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011;50(3):261–6.PubMedCrossRefGoogle Scholar
  167. 167.
    van Marke de Lumen K, Kedziora-Kornatowska K, Czuczejko J, Szewczyk-Golec K, Pawluk H, Motyl J, et al. Time dependent effect of melatonin administration on lipid peroxidation, superoxide dismutase activity and melatonin concentration in the elderly patients with essential arterial hypertension. Przegl Lek. 2008;65(6):273–6.Google Scholar
  168. 168.
    Tomas-Zapico C, Coto-Montes A. A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes. J Pineal Res. 2005;39(2):99–104.PubMedCrossRefGoogle Scholar
  169. 169.
    Pechánová O, Zicha J, Paulis L, Zenebe W, Dobesová Z, Kojsová S, et al. The effect of N-acetylcysteine and melatonin in adult spontaneously hypertensive rats with established hypertension. Eur J Pharmacol. 2007;561(1–3):129–36.PubMedCrossRefGoogle Scholar
  170. 170.
    Waki H, Gouraud SS, Maeda M, Raizada MK, Paton JFR. Contributions of vascular inflammation in the brainstem for neurogenic hypertension. Respir Physiol Neurobiol. 2011;178(3):422–8.PubMedCrossRefGoogle Scholar
  171. 171.
    Waki H, Gouraud SS, Maeda M, Paton JFR. Specific inflammatory condition in nucleus tractus solitarii of the SHR: novel insight for neurogenic hypertension? Auton Neurosci. 2008;142(1–2):25–31.PubMedCrossRefGoogle Scholar
  172. 172.
    Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR. Melatonin-a pleiotropic, orchestrating regulator molecule. Prog Neurobiol. 2011 Mar;93(3):350–84.PubMedCrossRefGoogle Scholar
  173. 173.
    Pevet P, Challet E. Melatonin: both master clock output and internal time-giver in the circadian clocks network. J Physiol Paris. 2011 Dec;105(4–6):170–82.PubMedCrossRefGoogle Scholar
  174. 174.
    Nava M, Quiroz Y, Vaziri N, Rodriguez-Iturbe B. Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats. Am J Physiol Renal Physiol. 2003;284(3):F447–54.PubMedCrossRefGoogle Scholar
  175. 175.
    Quiroz Y, Ferrebuz A, Romero F, Vaziri ND, Rodriguez-Iturbe B. Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reduction. Am J Physiol Ren Physiol. 2008;294(2):F336–44.CrossRefGoogle Scholar
  176. 176.
    Cheng MC, Wu TH, Huang LT, Tain YL. Renoprotective effects of melatonin in young spontaneously hypertensive rats with L-NAME. Pediatr Neonatol. 2014;55(3):189–95.PubMedCrossRefGoogle Scholar
  177. 177.
    Qiao YF, Guo WJ, Li L, Shao S, Qiao X, Shao JJ, et al. Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats. Mol Med Rep. 2016;13(1):21–6.PubMedCrossRefGoogle Scholar
  178. 178.
    Chen KH, Chen CH, Wallace CG, Chen YT, Yang CC, Sung PH, et al. Combined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome. Am J Transl Res. 2017;9(2):214–29.PubMedPubMedCentralGoogle Scholar
  179. 179.
    Tain YL, Lee CT, Chan JYH, Hsu CN. Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring. Am J Obstet Gynecol. 2016;215(5):636.e1–636.e72.CrossRefGoogle Scholar
  180. 180.
    Benigni A, Corna D, Zoja C, Sonzogni A, Latini R, Salio M, et al. Disruption of the Ang II type 1 receptor promotes longevity in mice. J Clin Investig. 2009;119(3):524–30.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Chen Y, Qing W, Sun M, Lv L, Guo D, Jiang Y. Melatonin protects hepatocytes against bile acid-induced mitochondrial oxidative stress via the AMPK-SIRT3-SOD2 pathway. Free Radic Res. 2015;49(10):1275–84.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Natalia Jorgelina Prado
    • 1
  • León Ferder
    • 2
  • Walter Manucha
    • 1
    • 3
  • Emiliano Raúl Diez
    • 1
    • 4
    Email author
  1. 1.Instituto de Medicina y Biología Experimental de Cuyo (IMBECU)Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)MendozaArgentina
  2. 2.Pediatric Department Nephrology Division, Miller School of MedicineUniversity of MiamiFloridaUSA
  3. 3.Área de Farmacología, Facultad de Ciencias MédicasUniversidad Nacional de CuyoMendozaArgentina
  4. 4.Instituto de Fisiología, Facultad de Ciencias MédicasUniversidad Nacional de CuyoMendozaArgentina

Personalised recommendations