Sodium pumps: ouabain, ion transport, and signaling in hypertension.

  title={Sodium pumps: ouabain, ion transport, and signaling in hypertension.},
  author={Mordecai P. Blaustein and John M. Hamlyn and Thomas L. Pallone},
  journal={American journal of physiology. Renal physiology},
  volume={293 1},
          F438; author reply F439
TO THE EDITOR: A recent Editorial Focus in this journal (7) addresses the newly recognized role of the sodium pump as both an ion transport protein and a hormone receptor with its own signaling cascade. The relative importance of the cardiotonic steroids (CTS) as endogenous signaling hormones versus their ability to inhibit the sodium pump is of great interest. Indeed, the article noted that “although all digitalislike compounds inhibit Na-K-ATPase-mediated transport, they differ considerably… 
Augmentation of Ouabain-Induced Increase in Heart Muscle Contractility by Akt Inhibitor MK-2206
A demonstration of the increase in the CS effect is demonstrated and the proposed Akt activity imposes a constant inhibitory force on muscle contraction, which is attenuated by low concentrations of MK-2206, resulting in potentiation of the ouabain effect.
P-Type Pumps: Na+,K+-ATPase
The Na + ,K + -ATPase, or sodium/potassium pump, is a ubiquitous protein in animal cell membrane. The Na + ,K + -ATPase couples the hydrolysis of one adenosine triphosphate (ATP) molecule to the
Chapter 4 Critical Roles of the Na + /K + -ATPase in Apoptosis and CNS Diseases
This chapter will outline the structure, function, and regulation of the Na/K-ATPase under normal as well as hypoxic/ischemic conditions, and outline the emerging role of ouabain and other Na/k-atPase inhibitors as endogenous hormones.
Oxidant Stress Amplification by Cardiotonic Steroids as Therapeutic Target in Chronic Kidney Disease and Heart Failure
The search for natriuretic hormones led to the discovery of endogenous cardiotonic steroids and their role in modulating renal sodium retention and blood pressure and they have also been implicated in organogenesis.
Formation of New High Density Glycogen-Microtubule Structures Is Induced by Cardiac Steroids*
It is shown that CS induces the formation of dark structures adjacent to the nucleus in human NT2 and ACHN cells, which are clusters of glycogen and a distorted microtubule network that may be part of a new type of cellular stress response.
Digibind Reverses Inhibition of Cellular Rb+ Uptake Caused by Endogenous Sodium Pump Inhibitors Present in Serum and Placenta of Women with Preeclampsia
These studies evidence EDLF in PE serum and Additionally, PE placentas have high EDLFs and may represent a source.
Ca2+ influx mechanisms in caveolae vesicles of pulmonary smooth muscle plasma membrane under inhibition of alpha2beta1 isozyme of Na+/K+-ATPase by ouabain.
Inhibition of alpha(2) isoform of Na(+)/K(+)-ATPase by ouabain plays a crucial role in modulating the Ca(2+) influx regulatory components in the caveolae microdomain for marked increase in (Ca(2+))(i) in the smooth muscle, which could be important for the manifestation of pulmonary hypertension.
Selective brain cooling in Arabian oryx (Oryx leucoryx): a physiological mechanism for coping with aridity?
Enhanced selective brain cooling in Arabian oryx supports the hypothesis that selective braincooling would bestow survival advantages for artiodactyl species inhabiting hot hyper-arid environments.
Reply to Blaustein et al.
The Editorial Focus “did not cite key articles that support the conclusion that CTS (cardiotonic steroids) hypertension is secondary to inhibition of sodium pumps,” according to the Blaustein et al.


PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension.
PST 2238 is a very potent compound that in MHS rats reduces blood pressure and normalizes Na-K pump alterations caused by a genetic alteration of the cytoskeletal adducin.
The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation.
It is demonstrated that the cardiac glycoside binding site of the alpha isoforms of the Na,K-ATPase have a physiological function and supports the hypothesis for a role of the endogenous cardiac Glycosides.
Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart.
Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo, and definitively illustrate a specific role for the alpha 2 Na, K- ATPase isoform in Ca2+ signaling during cardiac contraction.
The alpha2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice and increased vascular contractility in vitro.
It is demonstrated that the alpha2-isoform of the Na-K-ATPase mediates the ouabain-induced increase in vascular contractility, which could play a role in the development and maintenance of ouABain- induced hypertension.
Structure-Activity Relationships for the Hypertensinogenic Activity of Ouabain: Role of the Sugar and Lactone Ring
RHA and the unsaturated lactone ring are crucial to the high potency of OUA as an inhibitor of the sodium pump but appear to be unrelated to its ability to induce hypertension.
Sodium pump α2 subunits control myogenic tone and blood pressure in mice
A key question in hypertension is: How is long‐term blood pressure controlled? A clue is that chronic salt retention elevates an endogenous ouabain‐like compound (EOLC) and induces salt‐dependent
Chronic hypertension induced by ouabain but not digoxin in the rat: antihypertensive effect of digoxin and digitoxin.
It is suggested that sodium pump inhibition is not the exclusive mediator of the hemodynamic effects of these cardiac glycosides and the presence of structure-specific mechanisms that regulate their tissue levels and effects on long-term blood pressure is demonstrated.
Salt-sensitive hypertension is triggered by Ca2+ entry via Na+/Ca2+ exchanger type-1 in vascular smooth muscle
The findings indicate that salt-sensitive hypertension is triggered by Ca2+ entry through NCX1 in arterial smooth muscle and suggest thatNCX1 inhibitors might be useful therapeutically.
Membrane transport proteins: not just for transport anymore.
  • J. Kaunitz
  • Chemistry, Medicine
    American journal of physiology. Renal physiology
  • 2006
The Na-K-ATPase is identified as the molecular target of digitalis glucosides, and the only action attributed to digitalis at its molecular target was the inhibition of NaSO4.
Structure-activity relationships for the hypertensinogenic activity of ouabain: role of the sugar and lactone
  • ring. Hypertension
  • 2001