Magnesium sulfate potentiates effect of DigiFab on marinobufagenin-induced Na/K-ATPase inhibition.

Autor:	Zazerskaya IE; Institutes of Neonatology and Heart and Vessels, Almazov Federal Heart, Blood and Endocrinology Center, St. Petersburg, Russia;, Ishkaraeva VV; Institutes of Neonatology and Heart and Vessels, Almazov Federal Heart, Blood and Endocrinology Center, St. Petersburg, Russia;, Frolova EV; Sechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia;, Solodovnikova NG; Institutes of Neonatology and Heart and Vessels, Almazov Federal Heart, Blood and Endocrinology Center, St. Petersburg, Russia;, Grigorova YN; Institutes of Neonatology and Heart and Vessels, Almazov Federal Heart, Blood and Endocrinology Center, St. Petersburg, Russia; National Institute on Aging, National Institutes of Health, Baltimore, MD;, David Adair C; Department of Obstetrics and Gynecology, University of Tennessee, Chattanooga, Tennessee., Fedorova OV; National Institute on Aging, National Institutes of Health, Baltimore, MD;, Bagrov AY; National Institute on Aging, National Institutes of Health, Baltimore, MD; bagrova@mail.nih.gov.
Jazyk:	angličtina
Zdroj:	American journal of hypertension [Am J Hypertens] 2013 Nov; Vol. 26 (11), pp. 1269-72. Date of Electronic Publication: 2013 Jul 22.
DOI:	10.1093/ajh/hpt117
Abstrakt:	Background: Immunoneutralization of elevated circulating levels of endogenous digitalis-like Na/K-ATPase inhibitors (i.e. cardiotonic steroids (CTS)) represents a novel approach in the treatment of preeclampsia (PE). Recently we demonstrated that DigiFab (Fab fragments of affinity-purified ovine digoxin antibody) restores PE-induced inhibition of Na/K-ATPase in erythrocytes ex vivo. Previously magnesium ions were shown to antagonize digitalis-induced toxicity, which is mediated by Na/K-ATPase inhibition. We hypothesized that magnesium sulfate would potentiate the effect of DigiFab in the reversal of CTS-induced Na/K-ATPase inhibition. Methods: To test this hypothesis, we studied the ex vivo effect of DigiFab on Na/K-ATPase activity in erythrocytes from patients with PE in the absence and in the presence of 3 mmol/L magnesium sulfate. Results: Compared with 11 normotensive pregnant subjects (29 ± 1 years; gestational age = 39.0 ± 0.2 weeks; blood pressure = 111 ± 2/73 ± 2 mm Hg), the 12 patients with PE (30 ± 1 years; gestational age = 37.9 ± 0.3 weeks; blood pressure = 159 ± 5/99 ± 3 mm Hg) had plasma levels of marino-bufagenin increased 3-fold (1.38 ± 0.40 vs. 0.38 ± 0.10 nmol/L; P < 0.01) and activity of Na/K-ATPase in erythrocytes was inhibited (1.16 ± 0.11 vs. 2.80 ± 0.20 μmol Pi/ml/h; P < 0.01). Ex vivo, DigiFab (1 µg/ml) restored erythrocyte Na/K-ATPase activity (1.72 ± 0.13 µmol Pi/ml/h; P < 0.01), and 3 mmol magnesium sulfate potentiated the effect of DigiFab (2.30 ± 0.20 µmol Pi/ml/h; P < 0.01). Conclusions: Magnesium is capable of increasing the efficacy of immunoneutralization of marinobufagenin-induced Na/K-ATPase inhibition. (© Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
Databáze:	MEDLINE
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