Endogenous Ouabain

Hamlyn, John M.; Blaustein, Mordecai P.

doi:10.1161/hypertensionaha.116.06599

Cited by 64 publications

(50 citation statements)

References 101 publications

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“…[30][31][32] After performing experiments with nifedipine, ouabain was incubated in an organ bath to investigate the possible role of Na + / K + ATP-ase in smooth muscle calcium ion trafficking related to serotonin action. Ouabain is an endogenous cardiotonic steroid hormone produced in the adrenal cortex, 33 and it is believed to be involved in salt sensitivity and hypertension. 34 By blocking the N + /K + ATP-ase at the level of smooth muscle cells, an increase in intracellular calcium will occur, and the contraction of the smooth muscle will be possible.…”

Section: Discussionmentioning

confidence: 99%

Clarification of serotonin‐induced effects in peripheral artery disease observed through the femoral artery response in models of diabetes and vascular occlusion: The role of calcium ions

Stojanović

Prostran

Janković

et al. 2017

Clin Exp Pharma Physio

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Recent findings have demonstrated that serotonin is an important participant in the development and progression of peripheral artery diseases. Taking this into consideration, the goals of this study were to investigate the effects of serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic animals, with and without artery occlusion, with a particular focus on determining the role of calcium in this process. Contraction experiments with serotonin on intact and denuded femoral artery rings, in the presence or absence of nifedipine and ouabain (both separately, or in combination), as well as Ca -free Krebs-Ringer bicarbonate solution were performed. The serotonin-induced results were concentration dependent, but only in healthy animals. The endothelium-dependent contraction of the femoral artery was assessed. In healthy animals, the endothelium-reliant part of contraction was dependent on the extracellular calcium, while the smooth muscle-related part was instead dependent on the intracellular calcium. In diabetic animals, both nifedipine and ouabain influenced serotonin-induced vascular effects by blocking intracellular calcium pathways. However, this was diminished after the simultaneous administration of both blockers.

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Section: Discussionmentioning

confidence: 99%

Clarification of serotonin‐induced effects in peripheral artery disease observed through the femoral artery response in models of diabetes and vascular occlusion: The role of calcium ions

Stojanović

Prostran

Janković

et al. 2017

Clin Exp Pharma Physio

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“…Other diseases such as renal failure [118], preeclampsia [119], myocardial ischemia/infarction [120,121], and diabetes mellitus [122,123] were also observed in association with elevated levels of endogenous compounds in human plasma samples. However, the accurate measurement of endogenous digitalis compounds in human samples still faces big challenges [124]. …”

Section: Na/k-atpase As a Novel Target For Cardiac Fibrosismentioning

confidence: 99%

Reducing Cardiac Fibrosis: Na/K-ATPase Signaling Complex as a Novel Target

Fan

Xie

Tian

2017

Cardiovasc Pharm Open Access

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Cardiac fibrosis is a common pathological process in cardiac disease and may lead to heart failure. It can also cause sudden death even in those without cardiac symptoms. Tissue fibrosis can be categorized into two categories: replacement fibrosis (also called reparative fibrosis) and reactive fibrosis. In replacement fibrosis, infiltration of inflammatory cells and accumulation of Extracellular Matrix (ECM) proteins are the initial steps in forming scarlike fibrotic tissue after acute cardiac injury and cardiac cell necrosis. Reactive fibrosis can be formed in response to hormonal change and pressure or volume overload. Experimental studies in animals have identified important pathways such as the Renin-Angiotensin-Aldosterone System (RAAS) and the endothelin pathway that contribute to fibrosis formation. Despite the fact that clinical trials using RAAS inhibitors as therapies for reducing cardiac fibrosis and improving cardiac function have been promising, heart failure is still the leading cause of deaths in the United States. Intensive efforts have been made to find novel targets and to develop new treatments for cardiac fibrosis and heart failure in the past few decades. The Na/K-ATPase, a canonical ion transporter, has been shown to also function as a signal transducer and prolonged activation of Na/K-ATPase signaling has been found to promote the formation of cardiac fibrosis. Novel tools that block the activation of Na/K-ATPase signaling have been developed and have shown promise in reducing cardiac fibrosis. This review will discuss the recent development of novel molecular targets, focusing on the Na/K-ATPase signaling complex as a therapeutic target in treatment of cardiac fibrosis.

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“…A CTS was isolated from human plasma and was identified by mass spectrometry (MS) as endogenous ouabain (EO) or a ouabain isomer Mathews et al 1991). Nuclear magnetic resonance (NMR) and MS studies on human, bovine and rodent plasma and tissues verified that the endogenous substance is ouabain (Schneider et al 1998;Kawamura et al 1999;Komiyama et al 2000;Tashko et al 2010;Jacobs et al 2012;Hamlyn et al 2014); reviewed in Hamlyn & Blaustein, 2016). Moreover, recent studies identified two novel EO isomers that are not seen in commercial (plant) ouabain (Jacobs et al 2012;Hamlyn et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Pivotal role of α2 Na⁺ pumps and their high affinity ouabain binding site in cardiovascular health and disease

Blaustein

Chen

Hamlyn

et al. 2016

The Journal of Physiology

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Reduced smooth muscle (SM)-specific α2 Na pump expression elevates basal blood pressure (BP) and increases BP sensitivity to angiotensin II (Ang II) and dietary NaCl, whilst SM-α2 overexpression lowers basal BP and decreases Ang II/salt sensitivity. Prolonged ouabain infusion induces hypertension in rodents, and ouabain-resistant mutation of the α2 ouabain binding site (α2 mice) confers resistance to several forms of hypertension. Pressure overload-induced heart hypertrophy and failure are attenuated in cardio-specific α2 knockout, cardio-specific α2 overexpression and α2 mice. We propose a unifying hypothesis that reconciles these apparently disparate findings: brain mechanisms, activated by Ang II and high NaCl, regulate sympathetic drive and a novel neurohumoral pathway mediated by both brain and circulating endogenous ouabain (EO). Circulating EO modulates ouabain-sensitive α2 Na pump activity and Ca transporter expression and, via Na /Ca exchange, Ca homeostasis. This regulates sensitivity to sympathetic activity, Ca signalling and arterial and cardiac contraction.

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Endogenous Ouabain

Cited by 64 publications

References 101 publications

Clarification of serotonin‐induced effects in peripheral artery disease observed through the femoral artery response in models of diabetes and vascular occlusion: The role of calcium ions

Clarification of serotonin‐induced effects in peripheral artery disease observed through the femoral artery response in models of diabetes and vascular occlusion: The role of calcium ions

Reducing Cardiac Fibrosis: Na/K-ATPase Signaling Complex as a Novel Target

Pivotal role of α2 Na⁺ pumps and their high affinity ouabain binding site in cardiovascular health and disease

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Endogenous Ouabain

Cited by 64 publications

References 101 publications

Clarification of serotonin‐induced effects in peripheral artery disease observed through the femoral artery response in models of diabetes and vascular occlusion: The role of calcium ions

Clarification of serotonin‐induced effects in peripheral artery disease observed through the femoral artery response in models of diabetes and vascular occlusion: The role of calcium ions

Reducing Cardiac Fibrosis: Na/K-ATPase Signaling Complex as a Novel Target

Pivotal role of α2 Na+ pumps and their high affinity ouabain binding site in cardiovascular health and disease

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Pivotal role of α2 Na⁺ pumps and their high affinity ouabain binding site in cardiovascular health and disease