Ouabain, a circulating hormone secreted by the adrenals, is pivotal in cardiovascular disease. Fact or fantasy?

Abstract

Substantial evidence points to the presence in human plasma of an inhibitor of the sodium/potassium pump which plays a central role in the pathophysiology of circulatory disorders, including essential hypertension. Studies from the 1980/90s claimed that this inhibitor was identical or very similar in structure to plant-derived ouabain and was synthesized by the adrenal cortex. However, the physical evidence in studies reporting isolation and identification of ouabain in human plasma appears insecure on closer examination. Additionally, reported circulating levels of immunoreactive ouabain in humans vary greatly, the ability of the human adrenal glands to secrete ouabain is questionable and the original commercial assay for measuring immunoreactive ouabain is no longer available. We submit that the position of ouabain as an endogenous, adrenally produced regulator of the sodium pump is of such importance that the current evidence needs either to put on a more secure footing or to lose its current status.

Effect of global and regional sympathetic blockade on arterial pressure during water deprivation in conscious rats

“…On the other hand, release of adrenal cortical hormones during WD could also modulate activity of the sympathetic nervous system centrally and/or peripherally. The adrenocortical hormones corticosterone (47)(48)(49)(50)64), aldosterone (1,23,24,27,29), and endogenous oubain (2,5,35,36,40) all have the ability to influence SNA and affect arterial pressure. Additional studies are required to determine the role of these hormones in the regulation of arterial pressure during WD.…”

Advances in understanding the role of cardiac glycosides in control of sodium transport in renal tubules

“…Plant-derived cardiotonic steroids contain a five-membered lactone ring while the cardiotonic steroids of animal origin contain a six-membered lactone ring (Schoner & Scheiner-Bobis 2005). In humans, one cardiotonic steroid isolated from adrenal glands and plasma appears to be identical to plant-derived ouabain by NMR and mass spectroscopy (Nicholls et al 2009) and is designated as EO.…”

Ouabain downregulates Mcl-1 and sensitizes lung cancer cells to TRAIL-induced apoptosis

“…As ouabain has been found in human plasma (6, 9, 19 -20, 25-28) and identified as a human hormone (21,26), information regarding other activities of this compound is of great interest and will benefit both physiological and pathological knowledge. Although some studies have reported the apoptotic induction property of ouabain in cancer cells (4,11,23,35), the molecular basis of this induction and the precise role of this compound in TRAILmediated cancer cell death are not known.…”