Skip to main content
SpringerLink
Log in

The Role of CNS in the Effects of Salt on Blood Pressure

  • Secondary Hypertension: Nervous System Mechanisms (M Wyss, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Sympathetic nerve activity is involved in the pathogenesis of salt-sensitive hypertension. The central nervous system, which regulates sympathetic nerve activity and blood pressure, plays a pivotal role. Central sympathoexcitation is deeply involved in the pathogenesis of salt-sensitive hypertension, although the precise mechanisms have not been fully elucidated because of their complexity. The role of brain oxidative stress in sympathoexcitation has been suggested in some types of hypertensive animal models. We have shown that increased brain oxidative stress may elevate arterial pressure through central sympathoexcitation in salt-sensitive hypertension. Several other factors such as mineralocorticoid receptors, aldosterone, corticosterone, epithelial sodium channels, and angiotensin II also play important roles in central sympathetic activation, some of which can be associated with brain oxidative stress. Furthermore, brain paraventricular nucleus Gαi2-protein-mediated transduction has been recently reported as a candidate for the molecular mechanism countering the development of salt-sensitive hypertension.

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

Similar content being viewed by others

References

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

  1. Fujita T, Henry WL, Bartter FC, Lake CR, Delea CS. Factors influencing blood pressure in salt-sensitive patients with hypertension. Am J Med. 1980;69:334–44.

    Article  CAS  PubMed  Google Scholar 

  2. Ono A, Kuwaki T, Kumada M, Fujita T. Differential central modulation of the baroreflex by salt loading in normotensive and spontaneously hypertensive rats. Hypertension. 1997;29:808–14.

    Article  CAS  PubMed  Google Scholar 

  3. Fujita M, Ando K, Nagae A, Fujita T. Sympathoexcitation by oxidative stress in the brain mediates arterial pressure elevation in salt-sensitive hypertension. Hypertension. 2007;50:360–7.

    Article  CAS  PubMed  Google Scholar 

  4. Huang BS, Wang H, Leenen FH. Enhanced sympathoexcitatory and pressor responses to central Na+ in Dahl salt-sensitive vs. -resistant rats. Am J Physiol Heart Circ Physiol. 2001;281:H1881–9.

    CAS  PubMed  Google Scholar 

  5. Fujita M, Ando K, Kawarazaki H, Kawarasaki C, Muraoka K, Ohtsu H, et al. Sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in salt-induced chronic kidney disease. Hypertension. 2012;59:105–12.

    Article  CAS  PubMed  Google Scholar 

  6. Gomez-Sanchez EP, Gomez-Sanchez CM, Plonczynski M, Gomez-Sanchez CE. Aldosterone synthesis in the brain contributes to Dahl salt-sensitive rat hypertension. Exp Physiol. 2010;95:120–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Huang BS, White RA, Jeng AY, Leenen FH. Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats. Am J Physiol Regul Integr Comp Physiol. 2009;296:R994–1000.

    Article  CAS  PubMed  Google Scholar 

  8. Huang BS, Leenen FH. Mineralocorticoid actions in the brain and hypertension. Curr Hypertens Rep. 2011;13:214–20.

    Article  CAS  PubMed  Google Scholar 

  9. Ito K, Hirooka Y, Sunagawa K. Blockade of mineralocorticoid receptors improves salt-induced left-ventricular systolic dysfunction through attenuation of enhanced sympathetic drive in mice with pressure overload. J Hypertens. 2010;28:1449–58.

    Article  CAS  PubMed  Google Scholar 

  10. Ito K, Hirooka Y, Sunagawa K. Corticosterone-activated mineralocorticoid receptor contributes to salt-induced sympathoexcitation in pressure overload mice. Clin Exp Hypertens. 2014;36:550–6.

    Article  CAS  PubMed  Google Scholar 

  11. Nakano M, Hirooka Y, Matsukawa R, Ito K, Sunagawa K. Mineralocorticoid receptors/epithelial Na+ channels in the choroid plexus are involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats. Hypertens Res. 2013;36:277–84.

    Article  CAS  PubMed  Google Scholar 

  12. Van Huysse JW, Amin MS, Yang B, Leenen FH. Salt-induced hypertension in a mouse model of Liddle syndrome is mediated by epithelial sodium channels in the brain. Hypertension. 2012;60:691–6.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Huang BS, Leenen FH. Both brain angiotensin II and “ouabain” contribute to sympathoexcitation and hypertension in Dahl S rats on high salt intake. Hypertension. 1998;32:1028–33.

    Article  CAS  PubMed  Google Scholar 

  14. Leenen FH. The central role of the brain aldosterone-“ouabain” pathway in salt-sensitive hypertension. Biochim Biophys Acta. 1802;2010:1132–9.

    Google Scholar 

  15. Zimmerman MC, Lazartigues E, Sharma RV, Davisson RL. Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circ Res. 2004;95:210–6.

    Article  CAS  PubMed  Google Scholar 

  16. Kishi T, Hirooka Y, Sunagawa K. Sympathoinhibition caused by orally administered telmisartan through inhibition of the AT1 receptor in the rostral ventrolateral medulla of hypertensive rats. Hypertens Res. 2012;35:940–6.

    Article  CAS  PubMed  Google Scholar 

  17. Fujita M, Fujita T. The role of CNS in salt-sensitive hypertension. Curr Hypertens Rep. 2013;15:390–4. This is the previous review about the role of CNS in salt-sensitive hypertension, mainly focusing on our findings.

    Article  CAS  PubMed  Google Scholar 

  18. Gabor A, Leenen FH. Central neuromodulatory pathways regulating sympathetic activity in hypertension. J Appl Physiol (1985). 2012;113:1294–303.

    Article  Google Scholar 

  19. Wang JM, Veerasingham SJ, Tan J, Leenen FH. Effects of high salt intake on brain AT1 receptor densities in Dahl rats. Am J Physiol Heart Circ Physiol. 2003;285:H1949–55.

    Article  CAS  PubMed  Google Scholar 

  20. Wang H, Leenen FH. Brain sodium channels mediate increases in brain “ouabain” and blood pressure in Dahl S rats. Hypertension. 2002;40:96–100.

    Article  CAS  PubMed  Google Scholar 

  21. Ito K, Hirooka Y, Sunagawa K. Acquisition of brain na sensitivity contributes to salt-induced sympathoexcitation and cardiac dysfunction in mice with pressure overload. Circ Res. 2009;104:1004–11.

    Article  CAS  PubMed  Google Scholar 

  22. Leenen FH, Hou X, Wang HW, Ahmad M. Enhanced expression of epithelial sodium channels causes salt-induced hypertension in mice through inhibition of the alpha2-isoform of Na+, K+-ATPase. Physiol Rep. 2015;3(5):e12383: 1–9.

  23. Ogihara T, Asano T, Ando K, Sakoda H, Anai M, Shojima N, et al. High-salt diet enhances insulin signaling and induces insulin resistance in Dahl salt-sensitive rats. Hypertension. 2002;40:83–9.

    Article  CAS  PubMed  Google Scholar 

  24. Chen J, Gu D, Huang J, Rao DC, Jaquish CE, Hixson JE, et al. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in china: a dietary intervention study. Lancet. 2009;373:829–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Uzu T, Kimura G, Yamauchi A, Kanasaki M, Isshiki K, Araki S, et al. Enhanced sodium sensitivity and disturbed circadian rhythm of blood pressure in essential hypertension. J Hypertens. 2006;24:1627–32.

    Article  CAS  PubMed  Google Scholar 

  26. Kishi T, Hirooka Y, Konno S, Sunagawa K. Angiotensin II receptor blockers improve endothelial dysfunction associated with sympathetic hyperactivity in metabolic syndrome. J Hypertens. 2012;30:1646–55.

    Article  CAS  PubMed  Google Scholar 

  27. Nagae A, Fujita M, Kawarazaki H, Matsui H, Ando K, Fujita T. Sympathoexcitation by oxidative stress in the brain mediates arterial pressure elevation in obesity-induced hypertension. Circulation. 2009;119:978–86.

    Article  CAS  PubMed  Google Scholar 

  28. Kishi T, Hirooka Y. Sympathoexcitation associated with renin-angiotensin system in metabolic syndrome. Int J Hypertens. 2013;2013:406897.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Konno S, Hirooka Y, Kishi T, Sunagawa K. Sympathoinhibitory effects of telmisartan through the reduction of oxidative stress in the rostral ventrolateral medulla of obesity-induced hypertensive rats. J Hypertens. 2012;30:1992–9.

    Article  CAS  PubMed  Google Scholar 

  30. Wainford RD, Carmichael CY, Pascale CL, Kuwabara JT. Gαi2-protein-mediated signal transduction: central nervous system molecular mechanism countering the development of sodium-dependent hypertension. Hypertension. 2015;65:178–86. This is the remarkable article that has reported findings suggesting that the lack of PVN Gαi 2 -protein upregulation in response to salt intake reflects an underlying central mechanism driving the development of salt-sensitive hypertension.

  31. Kapusta DR, Pascale CL, Kuwabara JT, Wainford RD. Central nervous system Gαi2-subunit proteins maintain salt resistance via a renal nerve-dependent sympathoinhibitory pathway. Hypertension. 2013;61:368–75.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology and Endocrinology, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Megumi Fujita

  2. Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan

    Toshiro Fujita

Authors
  1. Megumi Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshiro Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Megumi Fujita.

Ethics declarations

Conflict of Interest

Dr. Toshiro Fujita has received research support from Takeda, Daiich-Sankyo, MSD, Boehringer Ingelheim, Mitsubishi Tanabe, Mochida, Omron, Fukuda-Denshi, Kyowa-Kirin, Toray, Astellas, and Chugai and consulting fees and honoraria from Takeda, Novartis, Boehringer Ingelheim, and Astellas. Dr. Megumi Fujita has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Sources of Funding

This work was supported by grants from the Japan Society for the Promotion of Science (No. 24591226), the Japan Heart Foundation Research Grant, Salt Science Research Foundation (No. 1234), and the Japan Vascular Disease Research Foundation.

Additional information

This article is part of the Topical Collection on Secondary Hypertension: Nervous System Mechanisms

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fujita, M., Fujita, T. The Role of CNS in the Effects of Salt on Blood Pressure. Curr Hypertens Rep 18, 10 (2016). https://doi.org/10.1007/s11906-015-0620-7

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11906-015-0620-7

Keywords

Search

Navigation