Skip to main content
SpringerLink
Log in

Mechanisms mediating renal sympathetic nerve activation in obesity-related hypertension

Mechanismen der Aktivierung des renalen N. sympathicus bei adipositasbedingter Hypertonie

  • Review article
  • Published:
Herz Aims and scope Submit manuscript

Abstract

Excessive renal sympathetic nerve activation may be one of the mechanisms underlying obesity-related hypertension. Impaired baroreflex sensitivity, adipokine disorders—such as leptin, adiponectin, and resistin—activation of the renin-angiotensin system, hyperinsulinemia, insulin resistance, and renal sodium retention present in obesity increase renal sympathetic nerve activity, thus contributing to the development of hypertension. Renal sympathetic denervation reduces both renal sympathetic activity and blood pressure in patients with obesity-related hypertension.

Zusammenfassung

Eine ausgeprägte Aktivierung des renalen N. sympathikus ist möglicherweise einer der Mechanismen, die der adipositasbedingten Hypertonie zugrunde liegen. Durch eine beeinträchtigte Baroreflexempfindlichkeit, Störungen der Adipokine, wie Leptin, Adiponektin und Resistin, Aktivierung des Renin-Angiotensin-Systems, Hyperinsulinämie und Insulinresistenz sowie die renale Natriumretention bei Adipositas kommt es zu einem Anstieg der renalen Sympathikusaktivität, was zur Entstehung der Hypertonie beiträgt. Die renale Sympathikusdenervation senkt sowohl die renale Sympathikusaktivität als auch den Blutdruck bei Patienten mit adipositasbedingter Hypertonie.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Popkin BM, Adair LS, Ng SW (2012) Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 70:3–21

    Article  PubMed Central  PubMed  Google Scholar 

  2. Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief 82:1–8

    PubMed  Google Scholar 

  3. Popkin BM, Doak CM (1998) The obesity epidemic is a worldwide phenomenon. Nutr Rev 56:106–114

    Article  CAS  PubMed  Google Scholar 

  4. Li XY, Jiang Y, Hu N et al (2012) Prevalence and characteristic of overweight and obesity among adults in China, 2010. Zhonghua Yu Fang Yi Xue Za Zhi 46:683–686

    PubMed  Google Scholar 

  5. Chiang BN, Perlman LV, Epstein FH (1969) Overweight and hypertension. A review. Circulation 39:403–421

    Article  CAS  PubMed  Google Scholar 

  6. Must A, Spadano J, Coakley EH et al (1999) The disease burden associated with overweight and obesity. JAMA 282:1523–1529

    Article  CAS  PubMed  Google Scholar 

  7. Wilson PW, D’Agostino RB, Sullivan L et al (2002) Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med 162:1867–1872

    Article  PubMed  Google Scholar 

  8. Doll S, Paccaud F, Bovet P et al (2002) Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries. Int J Obes Relat Metab Disord 26:48–57

    Article  CAS  PubMed  Google Scholar 

  9. Mokdad AH, Ford ES, Bowman BA et al (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289:76–79

    Article  PubMed  Google Scholar 

  10. Adair LS (2004) Dramatic rise in overweight and obesity in adult filipino women and risk of hypertension. Obes Res 12(8):1335–1341

    Article  PubMed  Google Scholar 

  11. Hwang LC, Bai CH, Sun CA, Chen CJ (2012) Prevalence of metabolically healthy obesity and its impacts on incidences of hypertension, diabetes and the metabolic syndrome in Taiwan. Asia Pac J Clin Nutr 21:227–233

    CAS  PubMed  Google Scholar 

  12. Kotsis V, Stabouli S, Bouldin M et al (2005) Impact of obesity on 24-hour ambulatory blood pressure and hypertension. Hypertension 45:602–607

    Article  CAS  PubMed  Google Scholar 

  13. Esler MD, Eikelis N, Lambert E, Straznicky N (2008) Neural mechanisms and management of obesity-related hypertension. Curr Cardiol Rep 10:456–463

    Article  PubMed  Google Scholar 

  14. Esler M, Jennings G, Korner P et al (1988) Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 11:3–20

    Article  CAS  PubMed  Google Scholar 

  15. Grassi G, Seravalle G, Brambilla G, Mancia G (2012) The sympathetic nervous system and new nonpharmacologic approaches to treating hypertension: a focus on renal denervation. Can J Cardiol 28:311–317

    Article  PubMed  Google Scholar 

  16. Prior LJ, Eikelis N, Armitage JA et al (2010) Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension 55:862–868

    Article  CAS  PubMed  Google Scholar 

  17. Da Silva Mattos AM, Xavier CH, Karlen-Amarante M et al (2012) Renal sympathetic nerve activity is increased in monosodium glutamate induced hyperadipose rats. Neurosci Lett 522:118–122

    Article  Google Scholar 

  18. Armitage JA, Burke SL, Prior LJ et al (2012) Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet. Hypertension 60:163–171

    Article  CAS  PubMed  Google Scholar 

  19. Rumantir MS, Vaz M, Jennings GL et al (1999) Neural mechanisms in human obesity-related hypertension. J Hypertens 17:1125–1133

    Article  CAS  PubMed  Google Scholar 

  20. Meredith IT, Friberg P, Jennings GL et al (1991) Exercise training lowers resting renal but not cardiac sympathetic activity in humans. Hypertension 18:575–582

    Article  CAS  PubMed  Google Scholar 

  21. Kassab S, Kato T, Wilkins FC et al (1995) Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension 25:893–897

    Article  CAS  PubMed  Google Scholar 

  22. Lohmeier TE, Iliescu R, Liu B et al (2012) Systemic and renal-specific sympathoinhibition in obesity hypertension. Hypertension 59:331–338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Schreihofer AM, Mandel DA, Mobley SC, Stepp DW (2007) Impairment of sympathetic baroreceptor reflexes in obese Zucker rats. Am J Physiol Heart Circ Physiol 293:H2543–H2549

    Article  CAS  PubMed  Google Scholar 

  24. Davis G (2011) Baroreflex and somato-reflex control of blood pressure, heart rate and renal sympathetic nerve activity in the obese Zucker rat. Exp Physiol 96:623–634

    Article  PubMed  Google Scholar 

  25. Skrapari I, Tentolouris N, Perrea D et al (2007) Baroreflex sensitivity in obesity: relationship with cardiac autonomic nervous system activity. Obesity (Silver Spring) 15:1685–1693

    Google Scholar 

  26. Grassi G, Seravalle G, Colombo M et al (1998) Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans. Circulation 97:2037–2042

    Article  CAS  PubMed  Google Scholar 

  27. Lakka TA, Lakka HM, Salonen R et al (2001) Abdominal obesity is associated with accelerated progression of carotid atherosclerosis in men. Atherosclerosis 154:497–504

    Article  CAS  PubMed  Google Scholar 

  28. Ciccone M, Vettor R, Pannacciulli N et al (2001) Plasma leptin is independently associated with the intima-media thickness of the common carotid artery. Int J Obes Relat Metab Disord 25:805–810

    Article  CAS  PubMed  Google Scholar 

  29. Thomas GN, Chook P, Qiao M et al (2004) Deleterious impact of “high normal” glucose levels and other metabolic syndrome components on arterial endothelial function and intima-media thickness in apparently healthy Chinese subjects: the CATHAY study. Arterioscler Thromb Vasc Biol 24:739–743

    Article  CAS  PubMed  Google Scholar 

  30. Lucini D, Cusumano G, Bellia A et al (2006) Is reduced baroreflex gain a component of the metabolic syndrome? Insights from the LINOSA study. J Hypertens 24:361–370

    Article  CAS  PubMed  Google Scholar 

  31. Keaney JJ, Larson MG, Vasan RS et al (2003) Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham study. Arterioscler Thromb Vasc Biol 23:434–439

    Article  CAS  PubMed  Google Scholar 

  32. Monahan KD, Eskurza I, Seals DR (2004) Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men. Am J Physiol Heart Circ Physiol 286:H2113–H2117

    Article  CAS  PubMed  Google Scholar 

  33. Fardin NM, Oyama LM, Campos RR (2012) Changes in baroreflex control of renal sympathetic nerve activity in high-fat-fed rats as a predictor of hypertension. Obesity (Silver Spring) 20:1591–1597

    Google Scholar 

  34. Tanida M, Shen J, Horii Y et al (2007) Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats. Exp Biol Med (Maywood) 232:390–397

    Google Scholar 

  35. Kosari S, Rathner JA, Badoer E (2012) Central resistin enhances renal sympathetic nerve activity via phosphatidylinositol 3-kinase but reduces the activity to brown adipose tissue via extracellular signal-regulated kinase1/2. J Neuroendocrinol 24:1432–1439

    Article  CAS  PubMed  Google Scholar 

  36. Harlan SM, Morgan DA, Agassandian K et al (2011) Ablation of the leptin receptor in the hypothalamic arcuate nucleus abrogates leptin-induced sympathetic activation. Circ Res 108:808–812

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Harlan SM, Morgan DA, Dellsperger DJ et al (2011) Cardiovascular and sympathetic effects of disrupting tyrosine 985 of the leptin receptor. Hypertension 57:627–632

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Hilzendeger AM, Morgan DA, Brooks L et al (2012) A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity. Am J Physiol Heart Circ Physiol 303:H197–H206

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Morgan DA, Thedens DR, Weiss R, Rahmouni K (2008) Mechanisms mediating renal sympathetic activation to leptin in obesity. Am J Physiol Regul Integr Comp Physiol 295:R1730–R1736

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Villarreal D, Reams G, Freeman RH (2000) Effects of renal denervation on the sodium excretory actions of leptin in hypertensive rats. Kidney Int 58:989–994

    Article  CAS  PubMed  Google Scholar 

  41. Gálvez-Prieto B, Bolbrinker J, Stucchi P et al (2008) Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue. J Endocrinol 197:55–64

    Article  PubMed  Google Scholar 

  42. Massiera F, Bloch-Faure M, Ceiler D et al (2001) Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J 15:2727–2729

    CAS  PubMed  Google Scholar 

  43. Boustany CM, Bharadwaj K, Daugherty A et al (2004) Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertension. Am J Physiol Regul Integr Comp Physiol 287:R943–R949

    Article  CAS  PubMed  Google Scholar 

  44. Gupte M, Boustany-Kari CM, Bharadwaj K et al (2008) ACE2 is expressed in mouse adipocytes and regulated by a high-fat diet. Am J Physiol Regul Integr Comp Physiol 295:R781–R788

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Boustany CM, Brown DR, Randall DC, Cassis LA (2005) AT1-receptor antagonism reverses the blood pressure elevation associated with diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 289:R181–R186

    Article  CAS  PubMed  Google Scholar 

  46. Gorzelniak K, Engeli S, Janke J et al (2002) Hormonal regulation of the human adipose-tissue renin-angiotensin system: relationship to obesity and hypertension. J Hypertens 20:965–973

    Article  CAS  PubMed  Google Scholar 

  47. Engeli S, Bohnke J, Gorzelniak K et al (2005) Weight loss and the renin-angiotensin-aldosterone system. Hypertension 45:356–362

    Article  CAS  PubMed  Google Scholar 

  48. Moretti JL, Burke SL, Davern PJ et al (2012) Renal sympathetic activation from long-term low-dose angiotensin II infusion in rabbits. J Hypertens 30:551–560

    Article  CAS  PubMed  Google Scholar 

  49. Crandall DL, Armellino DC, Busler DE et al (1999) Angiotensin II receptors in human preadipocytes: role in cell cycle regulation. Endocrinology 140:154–158

    Article  CAS  PubMed  Google Scholar 

  50. Ran J, Hirano T, Fukui T et al (2006) Angiotensin II infusion decreases plasma adiponectin level via its type 1 receptor in rats: an implication for hypertension-related insulin resistance. Metabolism 55:478–488

    Article  CAS  PubMed  Google Scholar 

  51. Han C, Liu J, Liu X, Li M (2010) Angiotensin II induces C-reactive protein expression through ERK1/2 and JNK signaling in human aortic endothelial cells. Atherosclerosis 212:206–212

    Article  CAS  PubMed  Google Scholar 

  52. Thatcher S, Yiannikouris F, Gupte M, Cassis L (2009) The adipose renin-angiotensin system: role in cardiovascular disease. Mol Cell Endocrinol 302:111–117

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Stucchi P, Cano V, Ruiz-Gayo M, Fernandez-Alfonso MS (2009) Aliskiren reduces body-weight gain, adiposity and plasma leptin during diet-induced obesity. Br J Pharmacol 158:771–778

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Linz D, Hohl M, Nickel A et al (2013) Effect of renal denervation on neurohumoral activation triggering atrial fibrillation in obstructive sleep apnea. Hypertension 62:767–774

    Article  CAS  PubMed  Google Scholar 

  55. Wang L, Lu CZ, Zhang X et al (2013) The effect of catheter based renal synthetic denervation on renin-angiotensin-aldosterone system in patients with resistant hypertension. Zhonghua Xin Xue Guan Bing Za Zhi 41:3–7

    PubMed  Google Scholar 

  56. Ezzahti M, Moelker A, Friesema EC et al (2014) Blood pressure and neurohormonal responses to renal nerve ablation in treatment-resistant hypertension. J Hypertens 32:135–141

    Article  CAS  PubMed  Google Scholar 

  57. Huggett RJ, Hogarth AJ, Mackintosh AF, Mary DA (2006) Sympathetic nerve hyperactivity in non-diabetic offspring of patients with type 2 diabetes mellitus. Diabetologia 49:2741–2744

    Article  CAS  PubMed  Google Scholar 

  58. Vollenweider P, Tappy L, Randin D et al (1993) Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans. J Clin Invest 92:147–154

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Rahmouni K, Haynes WG, Morgan DA, Mark AL (2003) Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin. J Neurosci 23:5998–6004

    CAS  PubMed  Google Scholar 

  60. Lu H, Duanmu Z, Scislo T, Dunbar JC (1998) The co-existence of insulin-mediated decreased mean arterial pressure and increased sympathetic nerve activity is not mediated by the baroreceptor reflex and differentially by hypoglycaemia. Clin Exp Hypertens 20:165–183

    Article  CAS  PubMed  Google Scholar 

  61. Morgan DA, Rahmouni K (2010) Differential effects of insulin on sympathetic nerve activity in agouti obese mice. J Hypertens 28:1913–1919

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Lim K, Burke SL, Head GA (2013) Obesity-related hypertension and the role of insulin and leptin in high-fat-fed rabbits. Hypertension 61:628–634

    Article  CAS  PubMed  Google Scholar 

  63. Takimoto C, Kumagai H, Osaka M et al (2008) Candesartan and insulin reduce renal sympathetic nerve activity in hypertensive type 1 diabetic rats. Hypertens Res 31:1941–1951

    Article  CAS  PubMed  Google Scholar 

  64. Schlaich MP, Straznicky N, Grima M et al (2011) Renal denervation: a potential new treatment modality for polycystic ovary syndrome? J Hypertens 29:991–996

    Article  CAS  PubMed  Google Scholar 

  65. Bickel CA, Verbalis JG, Knepper MA, Ecelbarger CA (2001) Increased renal Na-K-ATPase, NCC, and beta-ENaC abundance in obese Zucker rats. Am J Physiol Renal Physiol 281:F639–F648

    CAS  PubMed  Google Scholar 

  66. Kassab S, Patterson S, Wilkins FC et al (1994) Blunted natriuretic response to a high-sodium meal in obese dogs. Role of renal nerves. Hypertension 23:997–1001

    Article  CAS  PubMed  Google Scholar 

  67. Salman IM, Sattar MA, Ameer OZ et al (2010) Role of norepinephrine & angiotensin II in the neural control of renal sodium & water handling in spontaneously hypertensive rats. Indian J Med Res 131:786–792

    CAS  PubMed  Google Scholar 

  68. Shah S, Hussain T (2006) Enhanced angiotensin II-induced activation of Na+, K+-ATPase in the proximal tubules of obese Zucker rats. Clin Exp Hypertens 28:29–40

    Article  CAS  PubMed  Google Scholar 

  69. Millen AM, Norton GR, Majane OH et al (2013) Insulin resistance and the relationship between urinary Na(+)/K(+) and ambulatory blood pressure in a community of African ancestry. Am J Hypertens 26:708–716

    Article  CAS  PubMed  Google Scholar 

  70. Chavez-Canales M, Arroyo JP, Ko B et al (2013) Insulin increases the functional activity of the renal NaCl cotransporter. J Hypertens 31:303–311

    PubMed Central  CAS  PubMed  Google Scholar 

  71. Krieger DR, Landsberg L (1988) Mechanisms in obesity-related hypertension: role of insulin and catecholamines. Am J Hypertens 1:84–90

    CAS  PubMed  Google Scholar 

  72. Baudrand R, Campino C, Carvajal CA et al (2013) High sodium intake is associated with increased glucocorticoid production, insulin resistance and metabolic syndrome. Clin Endocrinol (Oxf) doi: 10.1111/cen.12225

    Google Scholar 

  73. Samuel P, Ali Q, Sabuhi R et al (2012) High Na intake increases renal angiotensin II levels and reduces expression of the ACE2-AT(2)R-MasR axis in obese Zucker rats. Am J Physiol Renal Physiol 303:F412–F419

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Guild SJ, McBryde FD, Malpas SC, Barrett CJ (2012) High dietary salt and angiotensin II chronically increase renal sympathetic nerve activity: a direct telemetric study. Hypertension 59:614–620

    Article  CAS  PubMed  Google Scholar 

  75. Katayama T, Sueta D, Kataoka K (2013) Long-term renal denervation normalizes disrupted blood pressure circadian rhythm and ameliorates cardiovascular injury in a rat model of metabolic syndrome. J Am Heart Assoc 2:e000197

    Article  PubMed Central  PubMed  Google Scholar 

  76. Krum H, Schlaich M, Whitbourn R et al (2009) Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 373:1275–1281

    Article  PubMed  Google Scholar 

  77. Schlaich MP, Hering D, Sobotka P et al (2012) Effects of renal denervation on sympathetic activation, blood pressure, and glucose metabolism in patients with resistant hypertension. Front Physiol 3:10

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a grant from the Key Science and Technology Projects in Hunan Province (2012SK2002), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20120162120098), and the Fundamental Research Funds for the Central Universities of Central South University (2012zzts121).

Compliance with ethical guidelines

Conflict of interest. The authors state that there are no conflicts of interest. The accompanying manuscript does not include studies on humans or animals.

Author information

Authors and Affiliations

  1. Department of Cardiology, The Third Xiangya Hospital, Central South University, 410013, Changsha, China

    W. Chen, S. Leo, C. Weng, X. Yang, Y. Wu & X. Tang MD, PhD

Authors
  1. W. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Leo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Weng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X. Tang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X. Tang MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, W., Leo, S., Weng, C. et al. Mechanisms mediating renal sympathetic nerve activation in obesity-related hypertension. Herz 40 (Suppl 2), 190–196 (2015). https://doi.org/10.1007/s00059-014-4072-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-014-4072-7

Keywords

Schlüsselwörter

Search

Navigation