Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

Bagrov, Alexei Y.; Shapiro, Joseph I.; Федорова, О. В.

doi:10.1124/pr.108.000711

Cited by 480 publications

(532 citation statements)

References 388 publications

(527 reference statements)

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“…5,6 The increased level of EO may have direct and indirect (via marinobufagenin) vasoconstrictor (hypertensive) effects by blocking sodium/potassium pump (Na þ /K þ -ATPase), consecutively increasing intracellular calcium level by the activation of the sodium-calcium exchanger, but this effect of EO is not homogenous, that is different Na þ /K þ -ATPase isoforms respond differently to EO. [7][8][9] Experimental use of low doses of ouabain increased arterial blood pressure in rats. 10 Beyond the classical effects of EO, the digitalis-like factors have genomic effects inducing hypertrophy in myocardial and vascular smooth muscle cells because of the activation of numerous known intracellular signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

et al. 2010

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According to previous studies endogenous ouabain (EO) closely correlates with high blood pressure, congestive heart failure and kidney disease in humans. Our aims were to analyse associations between plasma, urinary EO level and various markers of cardiovascular damage in treated hypertensive patients. Forty-one adult patients with hypertension and/or diabetes mellitus (DM) and/or chronic kidney disease (CKD) were studied. We assessed plasma and urinary EO, pro-brain natriuretic peptide and catecholamines, profile of ambulatory blood pressure monitor and cardiovascular status by echocardiography and echo-tracking. The highest level of plasma EO (19.7 ± 9.5 pmol l -1 ) was measured in hypertensive patients with DM and CKD. The nighttime mean arterial blood pressure independently correlated with the level of plasma EO (P ¼ 0.004), while independent predictor of the b-stiffness of carotid artery was the urinary EO (P ¼ 0.011). Elevated level of EO was associated with nighttime blood pressure and subclinical organ damage in treated hypertensive patients, suggesting possible role of EO in the pathogenesis of impaired diurnal blood pressure rhythm and arterial stiffness.

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Section: Introductionmentioning

confidence: 99%

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

et al. 2010

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“…As a result, downstream effectors are activated, resulting in the activation of protein kinase cascades and the generation of second messengers. This leads to a cascade that involves the generation of reactive oxygen species (ROS), activation of extracellular signal-regulated protein kinase (ERK) through activation of its mitogen-activated protein kinase (MEK), activation of phosphatidylinositol 3-kinase (PI3K), stimulation of endocytosis and activation of Akt, as well as activation of protein kinase C (22,34,35). This binding of ouabain to Na + ,K + -ATPase affects multiple cellular functions, thereby influencing cell growth, heart hypertrophy and apoptosis (22).…”

Section: Acute Effects Of Picomole Quantities Of Ouabain On Vascularmentioning

confidence: 99%

“…In addition, the acute hypertensinogenic effect of ouabain is attenuated in transgenic rats that are deficient in brain angiotensinogen (54). Therefore, in some diseases that are accompanied by an increased level of endogenous ouabain, such as hypertension (1), heart failure (55) and diabetes (35), the increase in sympathoexcitatory activity could be due to the actions of ouabain on the central reninangiotensin system. In addition to the sympathoexcitatory activity induced by ouabain via the central renin-angiotensinaldosterone pathway, D'Amico at al.…”

Section: Acute Effects Of Ouabain On the Central Nervous Systemmentioning

confidence: 99%

Hypertensive effects of the iv administration of picomoles of ouabain

Padilha

Salaíces

Vassallo

et al. 2011

Braz J Med Biol Res

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Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na + pump, inhibiting its activity. Inhibition of this pump increases intracellular Na + , which reduces the activity of the sarcolemmal Na + /Ca 2+ exchanger and thereby reduces Ca 2+ extrusion. Consequently, intracellular Ca 2+ increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.

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“…The role of this more recently discovered property in the hormone-like function of endogenous CTS and in the therapeutic effect of exogenous CTS in health and diseases is being increasingly recognized. Progress in the understanding of CTS action in the cardiovascular and nervous systems, metabolism, or cell growth and differentiation has been emphasized in recent reviews (1,2,40,42). -ATPase at the cell surface is important to both ion-pumping and receptor functions, and modulation of cellular Na ϩ -K ϩ -ATPase activity through changes in cell surface expression has been reported in response to major physiological or pathophysiological stimuli.…”

mentioning

confidence: 99%

Modulation of Na⁺-K⁺-ATPase cell surface abundance through structural determinants on the α1-subunit

Pierre

Belliard

Sottejeau

2011

American Journal of Physiology-Cell Physiology

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Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

Cited by 480 publications

References 388 publications

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

Hypertensive effects of the iv administration of picomoles of ouabain

Modulation of Na⁺-K⁺-ATPase cell surface abundance through structural determinants on the α1-subunit

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Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

Cited by 480 publications

References 388 publications

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

Hypertensive effects of the iv administration of picomoles of ouabain

Modulation of Na+-K+-ATPase cell surface abundance through structural determinants on the α1-subunit

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Modulation of Na⁺-K⁺-ATPase cell surface abundance through structural determinants on the α1-subunit