Pressor and vascular effects of cardiac glycosides

Kirch, Wilhelm

doi:10.1111/j.1365-2362.2001.00016.x

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…Because elevated levels of EO circulate in many patients with congestive heart failure (Gottlieb et al . ), treatment with digoxin would, based upon the dynamic ouabain–digoxin antagonism we describe, seem likely to promote vascular dilatation in patients – especially in those given lower doses of digoxin (Kirch, ; Rathore et al . ).…”

Section: Discussionmentioning

confidence: 95%

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Ouabain–digoxin antagonism in rat arteries and neurones

Song

Karashima

Hamlyn

et al. 2014

The Journal of Physiology

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Key pointsr 'Classic' cardiotonic steroids (CTSs) all inhibit Na + ,K + -ATPase (Na + pumps) and exert cardiotonic and vasotonic effects. Nevertheless, prolonged ouabain, but not digoxin, administration induces hypertension; moreover, digoxin antagonizes the hypertensinogenic effect of ouabain.r To examine acute ouabain-digoxin interactions, we tested these and related CTSs on myogenic tone (MT) in pressurized rat mesenteric small arteries and glutamate-evoked Ca 2+ transients in primary cultured rat hippocampal neurones.r The CTSs (0.3-10 nM) all augmented MT at 70 mmHg and Ca 2+ signals, but separated into two functional groups according to whether they were ouabain-or digoxin-like. CTSs within each group were synergistic, but between groups, were antagonistic to one another in both assays.r Na + pump αβ protomers may function as tetraprotomers ((αβ) 4 ) with quarter-site reactivity; simultaneous ouabain-and digoxin-like molecule binding promotes tetraprotomer disaggregation, enabling partial protomer reactivation.r These results may reveal why some patients respond poorly to digoxin therapy, and why Na + pumps may be a novel target for therapeutic development.Abstract 'Classic' cardiotonic steroids (CTSs) such as digoxin and ouabain selectively inhibit Na + ,K + -ATPase (the Na + pump) and, via Na + /Ca 2+ exchange (NCX), exert cardiotonic and vasotonic effects. CTS action is more complex than previously thought: prolonged subcutaneous administration of ouabain, but not digoxin, induces hypertension, and digoxin antagonizes ouabain's hypertensinogenic effect. We studied the acute interactions between CTSs in two indirect assays of Na + pump function: myogenic tone (MT) in isolated, pressurized rat mesenteric small arteries, and Ca 2+ signalling in primary cultured rat hippocampal neurones. The 'classic' CTSs (0.3-10 nM) behaved as 'agonists': all increased MT 70 (MT at 70 mmHg) and augmented glutamate-evoked Ca 2+ (Fura-2) signals. We then tested one CTS in the presence of another. Most CTSs could be divided into ouabain-like (ouabagenin, dihydroouabain (DHO), strophanthidin) or digoxin-like CTS (digoxigenin, digitoxin, bufalin). Within each group, the CTSs were synergistic, but ouabain-like and digoxin-like CTSs antagonized one another in both assays: For example, the ouabain-evoked (3 nM) increases in MT 70 and neuronal Ca 2+ signals were both greatly attenuated by the addition of 10 nM digoxin or 10 nM bufalin, and vice versa. Rostafuroxin (PST2238), a digoxigenin derivative that displaces 3 H-ouabain from Na + ,K + -ATPase, and attenuates some forms of hypertension, antagonized the effects of ouabain, but not digoxin. SEA0400, a Na + /Ca 2+ exchanger (NCX) blocker, antagonized the effects of both ouabain and digoxin. CTSs bind to the α subunit of pump αβ protomers. Analysis of potential models suggests that, in vivo, Na + pumps function as tetraprotomers ( (αβ) of a single CTS to one protomer blocks all pumping activity. The paradoxical ability of digoxin-like CTSs to reactivate the ouabain-inhibited com...

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Section: Discussionmentioning

confidence: 95%

“…C ). We suggest that the functional antagonism between ouabain and digoxin is relevant to the use of digitalis glycosides as a vasodilator in heart failure (Kirch, ).…”

Section: Discussionmentioning

confidence: 99%

Ouabain–digoxin antagonism in rat arteries and neurones

Song

Karashima

Hamlyn

et al. 2014

The Journal of Physiology

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Modulatory properties of cardiac and quercetin glycosides from Dacryodes edulis seeds during L-NAME-induced vascular perturbation

Amadi

Agomuo

Adumekwe

2020

Journal of Basic and Clinical Physiology and Pharmacology

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BackgroundNumerous food wastes have been identified to possess potent bioactive compounds used for the treatment of several diseases. Therefore this study evaluated the potentials of cardiac and quercetin glycosides extracted from Dacryodes edulis seeds to reverse vascular and endothelial damage (VAED).MethodsThe glycoside composition of the seeds was extracted using standard methods and characterized by gas chromatography. We then recruited rats with L-NAME-induced VAED based on confirmatory biomarkers cardiac troponin (CnT), cellular adhesion molecule (VCAM-1), lipoprotein associated phospholipase A2 (Lp-PLA2), RAAS, VWF, endothelin, eNOx, and homocysteine. Only rats that showed total alterations of all biomarkers were recruited into the respective experimental groups and treated with either metaprolol succinate (met.su) + losartan or glycoside extracts of D. edulis seeds (NPSG).ResultsChromatographic isolation of glycosides in the seed showed predominance of artemetin (1.59 mg/100 g), amygdalin (3.68 mg/100 g), digitoxin (19.21 mg/100 g), digoxin (27.23 mg/100 g), avicularin (133.59 mg/100 g), and hyperoside (481.76 mg/100 g). We observed decreased water intake and higher heart beats under vascular damage as the experiment progressed up to the fourth week. The met.su + losartan and H.D NPSG proved effective in restoring troponin, but both doses of NPSG normalized the VCAM-1 and RAAS activities excluding aldosterone and Lp-PLA2. Among the endothelial dysfunction biomarkers, H.D NPSG produced equivalent effects to met.su + losartan towards restoring the eNOx and VWF activities, but showed higher potency in normalizing the endothelin and Hcy levels.ConclusionsWe thus propose that the synergistic effect of the isolated glycosides from D. edulis shown in our study proved potent enough at high doses in treatment of vascular and endothelial dysfunction.

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Pressor and vascular effects of cardiac glycosides

Cited by 2 publications

References 17 publications

Ouabain–digoxin antagonism in rat arteries and neurones

Ouabain–digoxin antagonism in rat arteries and neurones

Modulatory properties of cardiac and quercetin glycosides from Dacryodes edulis seeds during L-NAME-induced vascular perturbation

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