Does the hormone “endogenous ouabain” exist in the human circulation?

Kaaja, Risto; Nicholls, M. Gary

doi:10.1002/biof.1421

Cited by 7 publications

(5 citation statements)

References 19 publications

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“…It is important to note that there remains some debate regarding the exact structure of EO [41]. Central to this debate, there is difficulty measuring the picomolar concentrations that exist in mammalian systems using direct chemical methods [42].…”

Section: Resultsmentioning

confidence: 99%

Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art

El‐Mallakh

Sampath²,

Horesh³

et al. 2022

IJMS

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Bipolar disorder (BD) is a severe psychiatric illness with a poor prognosis and problematic, suboptimal, treatments. Treatments, borne of an understanding of the pathoetiologic mechanisms, need to be developed in order to improve outcomes. Dysregulation of cationic homeostasis is the most reproducible aspect of BD pathophysiology. Correction of ionic balance is the universal mechanism of action of all mood stabilizing medications. Endogenous sodium pump modulators (collectively known as endogenous cardiac steroids, ECS) are steroids which are synthesized in and released from the adrenal gland and brain. These compounds, by activating or inhibiting Na+, K+-ATPase activity and activating intracellular signaling cascades, have numerous effects on cell survival, vascular tone homeostasis, inflammation, and neuronal activity. For the past twenty years we have addressed the hypothesis that the Na+, K+-ATPase-ECS system may be involved in the etiology of BD. This is a focused review that presents a comprehensive model pertaining to the role of ECS in the etiology of BD. We propose that alterations in ECS metabolism in the brain cause numerous biochemical changes that underlie brain dysfunction and mood symptoms. This is based on both animal models and translational human results. There are data that demonstrate that excess ECS induce abnormal mood and activity in animals, while a specific removal of ECS with antibodies normalizes mood. There are also data indicating that circulating levels of ECS are lower in manic individuals, and that patients with BD are unable to upregulate synthesis of ECS under conditions that increase their elaboration in non-psychiatric controls. There is strong evidence for the involvement of ion dysregulation and ECS function in bipolar illness. Additional research is required to fully characterize these abnormalities and define future clinical directions.

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Section: Resultsmentioning

confidence: 99%

Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art

El‐Mallakh

Sampath²,

Horesh³

et al. 2022

IJMS

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“…The existence of endogenous cardenolides, like EO, remains controversial to some [ 55 ] despite overwhelming evidence of its existence and physiological and pathological roles—some of which has been proven in studies using transgenic animals [ 21 ]. Many of the challenges related to the successful measurement of EO have been described elsewhere [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of endogenous ouabain by atrial natriuretic peptide is a guanylyl cyclase independent effect

et al. 2021

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Background Endogenous ouabain (EO) and atrial natriuretic peptide (ANP) are important in regulation of sodium and fluid balance. There is indirect evidence that ANP may be involved in the regulation of endogenous cardenolides. Methods H295R are human adrenocortical cells known to release EO. Cells were treated with ANP at physiologic concentrations or vehicle (0.1% DMSO), with or without guanylyl cyclase inhibitor 1,2,4 oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Cyclic guanosine monophosphate (cGMP), the intracellular second messenger of ANP, was measured by a chemiluminescent immunoassay and EO was measured by radioimmunoassay of C18 extracted samples. Results EO secretion is inhibited by ANP treatment, with the most prolonged inhibition (90 min vs ≤ 60 min) occurring at physiologic ANP concentrations (50 pg/mL). Inhibition of guanylyl cyclase with ODQ, also reduces EO secretion. The inhibitory effects on EO release in response to cotreatment with ANP and ODQ appeared to be additive. Conclusions ANP inhibits basal EO secretion, and it is unlikely that this is mediated through ANP-A or ANP-B receptors (the most common natriuretic peptide receptors) or their cGMP second messenger; the underlying mechanisms involved are not revealed in the current studies. The role of ANP in the control of EO synthesis and secretion in vivo requires further investigation.

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“…On the one hand, the secretion of EO is supposed to cause vasoconstriction and hypertension and thus could explain synergistic effects of aldosterone and high dietary salt intake. On the other hand, to date it is not even sure, if EO actually exists or not, as some research groups have been unable to detect EO in human circulation [58,71,72].…”

Section: Synergistic Effects Of Aldosterone Excess and High Salt Dietmentioning

confidence: 99%

Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism

et al. 2020

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First described in 1955 by Jerome W. Conn, primary aldosteronism (PA) today is well established as a relevant cause of secondary hypertension and accounts for about 5–10 % of hypertensives. The importance of considering PA is based on its deleterious target organ damage far beyond the effect of elevated blood pressure and on PA being a potentially curable form of hypertension. Aside the established contributory role of high dietary salt intake to arterial hypertension and cardiovascular disease, high salt intake is mandatory for aldosterone-mediated deleterious effects on target-organ damage in patients with primary aldosteronism. Consequently, counselling patients on the need to reduce salt intake represents a major component in the treatment of PA to minimize cardiovascular damage. Unfortunately, in PA patients salt intake is high and far beyond the target values of 5 g per day, recommended by the World Health Organization. Insufficient patient motivation for lifestyle interventions can be further complicated by enhancing effects of aldosterone on salt appetite, via central and gustatory pathways. In this context, treatment for PA by adrenalectomy results in a spontaneous decrease in dietary salt intake and might therefore provide further reduction of cardiovascular risk in PA than specific medical treatment alone. Furthermore, there is evidence from clinical studies that even after sufficient treatment of PA dietary salt intake remains a relevant prognostic factor for cardiovascular risk. This review will focus on the synergistic benefits derived from both blockade of aldosterone-mediated effects and reduction in dietary salt intake on cardiovascular risk.

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Does the hormone “endogenous ouabain” exist in the human circulation?

Cited by 7 publications

References 19 publications

Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art

Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art

Inhibition of endogenous ouabain by atrial natriuretic peptide is a guanylyl cyclase independent effect

Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism

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