Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Deregulation of adipokines related to target organ damage on resistant hypertension

Subjects

Abstract

Resistant hypertension (RHTN) includes patients with controlled blood pressure (BP) (CRHTN) and uncontrolled BP (UCRHTN). In fact, RHTN patients are more likely to have target organ damage (TOD), and resistin, leptin and adiponectin may affect BP control in these subjects. We assessed the relationship between adipokines levels and arterial stiffness, left ventricular hypertrophy (LVH) and microalbuminuria (MA). This cross-sectional study included CRHTN (n=51) and UCRHTN (n=38) patients for evaluating body mass index, ambulatory blood pressure monitoring, plasma adiponectin, leptin and resistin concentrations, pulse wave velocity (PWV), MA and echocardiography. Leptin and resistin levels were higher in UCRHTN, whereas adiponectin levels were lower in this same subgroup. Similarly, arterial stiffness, LVH and MA were higher in UCRHTN subgroup. Adiponectin levels negatively correlated with PWV (r=−0.42, P<0.01), and MA (r=−0.48, P<0.01) only in UCRHTN. Leptin was positively correlated with PWV (r=0.37, P=0.02) in UCRHTN subgroup, whereas resistin was not correlated with TOD in both subgroups. Adiponectin is associated with arterial stiffness and renal injury in UCRHTN patients, whereas leptin is associated with arterial stiffness in the same subgroup. Taken together, our results showed that those adipokines may contribute to vascular and renal damage in UCRHTN patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation 2008; 117: e510–e526.

    Article  Google Scholar 

  2. Vakili BA, Okin PM, Devereux RB . Prognostic implications of left ventricular hypertrophy. Am Heart J 2001; 141: 334–341.

    Article  CAS  Google Scholar 

  3. Vlek AL, van der Graaf Y, Spiering W, Algra A, Visseren FL . Cardiovascular events and all-cause mortality by albuminuria and decreased glomerular filtration rate in patients with vascular disease. J Intern Med 2008; 264: 351–360.

    Article  CAS  Google Scholar 

  4. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37: 1236–1241.

    Article  CAS  Google Scholar 

  5. Martins LC, Figueiredo VN, Quinaglia T, Boer-Martins L, Yugar-Toledo JC, Martin JF et al. Characteristics of resistant hypertension: ageing, body mass index, hyperaldosteronism, cardiac hypertrophy and vascular stiffness. J Hum Hypertens 2011; 25: 532–538.

    Article  CAS  Google Scholar 

  6. Quinaglia T, Martins LC, Figueiredo VN, Santos RC, Yugar-Toledo JC, Martin JF et al. Non-dipping pattern relates to endothelial dysfunction in patients with uncontrolled resistant hypertension. J Hum Hypertens 2011; 25: 656–664.

    Article  CAS  Google Scholar 

  7. Fonseca-Alaniz MH, Takada J, Alonso-Vale MI, Lima FB . Adipose tissue as an endocrine organ: from theory to practice. J Pediatr (Rio J) 2007; 83: S192–S203.

    Article  Google Scholar 

  8. Chow WS, Cheung BM, Tso AW, Xu A, Wat NM, Fong CH et al. Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year prospective study. Hypertension 2007; 49: 1455–1461.

    Article  CAS  Google Scholar 

  9. Schutte R, Huisman HW, Schutte AE, Malan NT . Leptin is independently associated with systolic blood pressure, pulse pressure and arterial compliance in hypertensive African women with increased adiposity: the POWIRS study. J Hum Hypertens 2005; 19: 535–541.

    Article  CAS  Google Scholar 

  10. Zhang L, Curhan GC, Forman JP . Plasma resistin levels associate with risk for hypertension among nondiabetic women. J Am Soc Nephrol 2010; 21: 1185–1191.

    Article  CAS  Google Scholar 

  11. Fang C, Lei J, Zhou SX, Zhang YL, Yuan GY, Wang JF . Association of higher resistin levels with inflammatory activation and endothelial dysfunction in patients with essential hypertension. Chin Med J (Engl) 2013; 126: 646–649.

    CAS  Google Scholar 

  12. Youn JC, Kim C, Park S, Lee SH, Kang SM, Choi D et al. Adiponectin and progression of arterial stiffness in hypertensive patients. Int J Cardiol 2011; 163 (3): 316–319.

    Article  Google Scholar 

  13. Hong SJ, Park CG, Seo HS, Oh DJ, Ro YM . Associations among plasma adiponectin, hypertension, left ventricular diastolic function and left ventricular mass index. Blood Press 2004; 13: 236–242.

    Article  CAS  Google Scholar 

  14. Wannamethee SG, Tchernova J, Whincup P, Lowe GD, Kelly A, Rumley A et al. Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease. Atherosclerosis 2007; 191: 418–426.

    Article  CAS  Google Scholar 

  15. Zhu W, Cheng KK, Vanhoutte PM, Lam KS, Xu A . Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci (Lond) 2008; 114: 361–374.

    Article  CAS  Google Scholar 

  16. Kartal O, Inal V, Baysan O, Saglam K . Relationship between serum leptin levels and left ventricular hypertrophy in obese hypertensive patients. Anatol J Cardiol 2008; 8: 342–346.

    Google Scholar 

  17. Schutte AE, Huisman HW, Schutte R, van Rooyen JM, Malan L, Fourie CMT et al. Adipokines and cardiometabolic function: How are they interlinked? Regul Peptides 2010; 164: 133–138.

    Article  CAS  Google Scholar 

  18. de Haro Moraes C, Figueiredo VN, de Faria AP, Barbaro NR, Sabbatini AR, Quinaglia T et al. High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension. J Hum Hypertens 2013; 27: 225–230.

    Article  CAS  Google Scholar 

  19. de Faria APC, Demacq C, Figueiredo VN, Moraes CH, Santos RC, Sabbatini AR et al. Hypoadiponectinemia and aldosterone excess are associated with lack of blood pressure control in subjects with resistant hypertension. Hypertens Res 2013; 36: 1067–1072.

    Article  CAS  Google Scholar 

  20. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27: 2588–2605.

    Article  Google Scholar 

  21. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005; 18 (12): 1440–1463.

    Article  Google Scholar 

  22. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: i–xii, 1–253.

  23. Ehrhart-Bornstein M, Arakelyan K, Krug AW, Scherbaum WA, Bornstein SR . Fat cells may be the obesity-hypertension link: human adipogenic factors stimulate aldosterone secretion from adrenocortical cells. Endocr Res 2004; 30: 865–870.

    Article  CAS  Google Scholar 

  24. Kadowaki T, Yamauchi T . Adiponectin and adiponectin receptors. Endocr Rev 2005; 26: 439–451.

    Article  CAS  Google Scholar 

  25. Zieman SJ, Melenovsky V, Kass DA . Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol 2005; 25: 932–943.

    Article  CAS  Google Scholar 

  26. Tsioufis C, Dimitriadis K, Chatzis D, Vasiliadou C, Tousoulis D, Papademetriou V et al. Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension. Am J Cardiol 2005; 96: 946–951.

    Article  CAS  Google Scholar 

  27. Tesauro M, Mascali A, Franzese O, Cipriani S, Cardillo C, Di Daniele N . Chronic kidney disease, obesity, and hypertension: the role of leptin and adiponectin. Int J Hypertens 2012; 2012: 943605.

    Article  CAS  Google Scholar 

  28. Meyer C, Robson D, Rackovsky N, Nadkarni V, Gerich J . Role of the kidney in human leptin metabolism. Am J Physiol 1997; 273: E903–E907.

    CAS  PubMed  Google Scholar 

  29. Pladevall M, Williams K, Guyer H, Sadurni J, Falces C, Ribes A et al. The association between leptin and left ventricular hypertrophy: a population-based cross-sectional study. J Hypertens 2003; 21: 1467–1473.

    Article  CAS  Google Scholar 

  30. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A . Resistin an adipokine with potent proinflammatory properties. J Immunol 2005; 174: 5789–5795.

    Article  CAS  Google Scholar 

  31. Windham BG, Griswold ME, Farasat SM, Ling SM, Carlson O, Egan JM et al. Influence of leptin, adiponectin, and resistin on the association between abdominal adiposity and arterial stiffness. Am J Hypertens 2010; 23: 501–507.

    Article  CAS  Google Scholar 

  32. Zorad S, Dou JT, Benicky J, Hutanu D, Tybitanclova K, Zhou J et al. Long-term angiotensin II AT(1) receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPAR-gamma. Eur J Pharmacol 2006; 552: 112–122.

    Article  CAS  Google Scholar 

  33. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Koh Y et al. Distinct vascular and metabolic effects of different classes of anti-hypertensive drugs. Int J Cardiol 2010; 140: 73–81.

    Article  Google Scholar 

  34. Ubaid-Girioli S, Ferreira-Melo SE, Souza LA, Nogueira EA, Yugar-Toledo JC, Coca A et al. Aldosterone escape with diuretic or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy in patients with mild to moderate hypertension. J Clin Hypertens (Greenwich) 2007; 9: 770–774.

    Article  CAS  Google Scholar 

  35. Sowers JR, Whaley-Connell A, Epstein M . Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension. Ann Intern Med 2009; 150: 776–783.

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by the State of São Paulo Research Foundation (FAPESP), SP, Brazil, National Council for Scientific and Technological Development (CNPq) and Coordination for Improvement of Higher Education Personnel (Capes), Brazil.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H Moreno.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sabbatini, A., Faria, A., Barbaro, N. et al. Deregulation of adipokines related to target organ damage on resistant hypertension. J Hum Hypertens 28, 388–392 (2014). https://doi.org/10.1038/jhh.2013.118

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2013.118

Keywords

This article is cited by

Search

Quick links