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Cited by 285Sodium Intake and HealthRenin-Angiotensin System StudiesBlood Pressure and Hypertension Studies

The DOI matches its Crossref record; 301 of the 301 references it cites were found in a registry or an index.

How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension

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Blaustein, Mordecai P., Leenen, Frans H. H., Chen, Ling, Golovina, Vera A., Hamlyn, John M., Pallone, Thomas L., Van Huysse, James W., Zhang, Jin, Wier, W. Gil·2012·American Journal of Physiology-Heart and Circulatory Physiology
DOI 10.1152/ajpheart.00899.2011PMC PMC3311458
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Abstract

Excess dietary salt is a major cause of hypertension. Nevertheless, the specific mechanisms by which salt increases arterial constriction and peripheral vascular resistance, and thereby raises blood pressure (BP), are poorly understood. Here we summarize recent evidence that defines specific molecular links between Na + and the elevated vascular resistance that directly produces high BP. In this new paradigm, high dietary salt raises cerebrospinal fluid [Na + ]. This leads, via the Na + -sensing circumventricular organs of the brain, to increased sympathetic nerve activity (SNA), a major trigger of vasoconstriction. Plasma levels of endogenous ouabain (EO), the Na + pump ligand, also become elevated. Remarkably, high cerebrospinal fluid [Na + ]-evoked, locally secreted (hypothalamic) EO participates in a pathway that mediates the sustained increase in SNA. This hypothalamic signaling chain includes aldosterone, epithelial Na + channels, EO, ouabain-sensitive α 2 Na + pumps, and angiotensin II (ANG II). The EO increases (e.g.) hypothalamic ANG-II type-1 receptor and NADPH oxidase and decreases neuronal nitric oxide synthase protein expression. The aldosterone-epithelial Na + channel-EO-α 2 Na + pump-ANG-II pathway modulates the activity of brain cardiovascular control centers that regulate the BP set point and induce sustained changes in SNA. In the periphery, the EO secreted by the adrenal cortex directly enhances vasoconstriction via an EO-α 2 Na + pump-Na + /Ca 2+ exchanger-Ca 2+ signaling pathway. Circulating EO also activates an EO-α 2 Na + pump-Src kinase signaling cascade. This increases the expression of the Na + /Ca 2+ exchanger-transient receptor potential cation channel Ca 2+ signaling pathway in arterial smooth muscle but decreases the expression of endothelial vasodilator mechanisms. Additionally, EO is a growth factor and may directly participate in the arterial structural remodeling and lumen narrowing that is frequently observed in established hypertension. These several central and peripheral mechanisms are coordinated, in part by EO, to effect and maintain the salt-induced elevation of BP.

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Research works printed but not linked: 20

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Metadata

Authors
Blaustein, M. P., Leenen, F. H. H., Chen, L., Golovina, V. A., Hamlyn, J. M., Pallone, T. L., Van Huysse, J. W., Zhang, J., & Wier, W. G.
Affiliations
  • University of Maryland, Baltimore (US)
  • Ottawa Heart Institute (CA)
  • the 4Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
Corresponding author
Blaustein, Mordecai P.
ORCID
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Publisher
American Physiological Society
Published
2012-03-01
Volume
302
Issue
5
Pages
H1031-H1049
ISSN
  • 0363-6135 (ISSN-L)
  • 1522-1539
DOI
10.1152/ajpheart.00899.2011
PMC
PMC3311458
OpenAlex
W2156773851
Cited by
285
References
301
Citations by year
2026: 6 · 2025: 9 · 2024: 12 · 2023: 18 · 2022: 14 · 2021: 12 · 2020: 15 · 2019: 17 · 2018: 20 · 2017: 19 · 2016: 23 · 2015: 22 · 2014: 49 · 2013: 32 · 2012: 15
FWCI
3.65
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Canadian Institutes of Health Research
  • National Heart, Lung, and Blood Institute (R01 HL09196, P01HL078870, R01HL107654, R01HL045215)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-67631, R37DK042495)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
salt-sensitive hypertension, dietary sodium, endogenous ouabain, Na+/Ca2+ exchanger, cerebrospinal fluid sodium, circumventricular organs, sympathetic activity, vasoconstriction, systemic vascular resistance, aldosterone, epithelial Na+ channel, angiotensin II type 1 receptor, NADPH oxidase, neuronal nitric oxide synthase, arterial smooth muscle, arterial remodeling, Src kinase signaling, TRP channels, blood pressure regulation
MeSH terms
Sodium-Potassium-Exchanging ATPase, Animals, Cardiotonic Agents, Female, Humans, Hypertension, Hypothalamus, Male, Ouabain, Pregnancy, Sympathetic Nervous System, Sodium Chloride, Dietary, Mice, Rats

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