Sodium pumps, ouabain and aldosterone in the brain: A neuromodulatory pathway underlying salt-sensitive hypertension and heart failure.

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  • Author(s): Leenen FHH;Leenen FHH; Wang HW; Wang HW; Hamlyn JM; Hamlyn JM
  • Source:
    Cell calcium [Cell Calcium] 2020 Mar; Vol. 86, pp. 102151. Date of Electronic Publication: 2019 Dec 17.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Review
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8006226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1991 (Electronic) Linking ISSN: 01434160 NLM ISO Abbreviation: Cell Calcium Subsets: MEDLINE
    • Publication Information:
      Publication: <2003->: Amsterdam : Elsevier
      Original Publication: [Edinburgh, New York] Churchill Livingston
    • Subject Terms:
      Aldosterone/*metabolism ; Brain/*metabolism ; Heart Failure/*metabolism ; Hypertension/*metabolism ; Ouabain/*metabolism ; Sodium Chloride, Dietary/*adverse effects ; Sodium-Potassium-Exchanging ATPase/*metabolism; Animals ; Heart Failure/blood ; Heart Failure/complications ; Heart Failure/physiopathology ; Humans ; Hypertension/blood ; Hypertension/complications ; Hypertension/physiopathology ; Ouabain/blood
    • Abstract:
      Accumulating evidence obtained over the last three decades has revealed a neuroendocrine system in the brain that mediates long term increases in blood pressure. The system involves distinct ion transport pathways including the alpha-2 isoform of the Na,K pump and epithelial sodium channels, as well as critical hormone elements such as angiotensin II, aldosterone, mineralocorticoid receptors and endogenous ouabain. Activation of this system either by circulating or central sodium ions and/or angiotensin II leads to a cascading sequence of events that begins in the hypothalamus and involves the participation of several brain nuclei including the subfornical organ, supraoptic and paraventricular nuclei and the rostral ventral medulla. Key events include heightened aldosterone synthesis and mineralocorticoid receptor activation, upregulation of epithelial sodium channels, augmented synthesis and secretion of endogenous ouabain from hypothalamic magnocellular neurons, and sustained increases in sympathetic outflow. The latter step depends upon increased production of angiotensin II and the primary amplification of angiotensin II type I receptor signaling from the paraventricular nucleus to the rostral ventral lateral medulla. The transmission of sympathetic traffic is secondarily amplified in the periphery by increased short- and long-term potentiation in sympathetic ganglia and by sustained actions of endogenous ouabain in the vascular wall that augment expression of sodium calcium exchange, increase cytosolic Ca 2+ and heighten myogenic tone and contractility. Upregulation of this multi-amplifier system participates in forms of hypertension where salt, angiotensin and/or aldosterone are elevated and contributes to adverse outcomes in heart failure.
      Competing Interests: Declaration of Competing Interest None.
      (Copyright © 2019 Elsevier Ltd. All rights reserved.)
    • Grant Information:
      FRN: MOP-74432 Canada CIHR
    • Contributed Indexing:
      Keywords: Brain; Calcium; Hypertension; Ouabain; Sodium potassium pump
    • Accession Number:
      0 (Sodium Chloride, Dietary)
      4964P6T9RB (Aldosterone)
      5ACL011P69 (Ouabain)
      EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
    • Publication Date:
      Date Created: 20200119 Date Completed: 20210601 Latest Revision: 20210601
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.ceca.2019.102151
    • Accession Number:
      31954234