Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia

Lopatin, Denis A.; Айламазян, Э. К.; Dmitrieva, Renata I.; Shpen, V.M.; Федорова, О. В.; Doris, Peter A.; Bagrov, Alexei Y.

doi:10.1097/00004872-199917080-00018

Cited by 176 publications

(179 citation statements)

References 33 publications

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“…After the introduction of assays for specific cardiotonic steroids, levels of endogenous ouabain and marinobufagenin were found to be increased by four-fold and eight-fold, respectively, in patients with severe pre-eclampsia. 52 In a study of women with milder pre-eclampsia, elevated levels of marinobufagenin accompanied inhibition of the Na + /K + -ATPase in erythrocytes, but endogenous ouabain levels were not markedly increased; ex vivo treatment of erythrocytes with an antimarinobufagenin antibody-but not an antiouabain antibody-reversed this inhibition. 142…”

Section: Role Of Cardiotonic Steroids In Pre-eclampsiamentioning

confidence: 99%

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Endogenous digitalis: pathophysiologic roles and therapeutic applications

2008

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SUMMARYEndogenous digitalis-like factors, also called cardiotonic steroids, have been thought for nearly half a century to have important roles in health and disease. The endogenous cardiotonic steroids ouabain and marinobufagenin have been identified in humans, and an effector mechanism has been delineated by which these hormones signal through the sodium/potassium-transporting ATPase. These findings have increased interest in this field substantially. Although cardiotonic steroids were first considered important in the regulation of renal sodium transport and arterial pressure, subsequent work has implicated these hormones in the control of cell growth, apoptosis and fibrosis, among other processes. This Review focuses on the role of endogenous cardiotonic steroids in the pathophysiology of essential hypertension, congestive heart failure, end-stage renal disease and pre-eclampsia. We also discuss potential therapeutic strategies that have emerged as a result of the increased understanding of the regulation and actions of cardiotonic steroids.

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Section: Role Of Cardiotonic Steroids In Pre-eclampsiamentioning

confidence: 99%

“…Finally, as a result of the identification of specific endogenous cardiotonic steroids, reliable immunoassays have been developed. 16,[48][49][50][51][52][53][54] …”

Section: Historical Perspectivementioning

confidence: 99%

Endogenous digitalis: pathophysiologic roles and therapeutic applications

2008

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“…One of the factors contributing to the pathogenesis of PE are CTS [3,10,11]. Pregnancy is associated with renal sodium retention [12,13], a major stimulus for MBG production [14].…”

Section: Introductionmentioning

confidence: 99%

“…In normal pregnancy, moderatly elevated levels of MBG do not alter vascular tone [10,13]. In patients with PE and in pregnant rats with PE-like symptoms, however, levels of MBG become substantially elevated and accompany inhibition of the NKA [11,13,15]. Accordingly, in rats with PE-like symptoms, in vivo administration of anti-MBG antibody reduced blood pressure and restored activity of the sodium pump in vascular sarcolemma [13].…”

Section: Introductionmentioning

confidence: 99%

Endogenous sodium pump inhibitors, diabetes mellitus and preeclampsia

et al. 2007

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Endogenous inhibitors of the Na/K-ATPase (NKA) and diabetes mellitus (DM) are both risk factors for preeclampsia and NaCl sensitive hypertension. Our goal was to test the hypothesis that NaCl supplementation, induces preeclampsia-like symptoms in pregnant rats with DM via stimulation of marinobufagenin (MBG), a natriuretic and vasoconstrictor inhibitor of the NKA. Type 2 DM in female Sprague-Dawley rats was induced by administration of 65 mg/kg streptozotocin at day 4 post partum. In intact rats, pregnancy was associated with a 2-fold increase in MBG levels and a mild impairment in glucose tolerance. Pregnant rats with DM exhibited fetal macrosomia, greater impairment of glucose tolerance, and higher levels of MBG as compared to that in normal pregnant rats. As compared to intact pregnant rats, NaCl supplementation of diabetic pregnant rats (drinking 1.8% NaCl during days 12-19 of pregnancy) was associated with an increase in systolic blood pressure, decreased fetal and placental weight, five-fold elevation of MBG excretion, and 42% inhibition of NKA in erythrocytes. In nonpregnant rats, in vivo pretreatment with anti-MBG antibody produced an exaggerated response of plasma levels of glucose and insulin in oral glucose tolerance test. These results suggest that MBG is a common factor in the pathogenesis of DM and preeclampsia, and that regulation of glucose tolerance may be one of the physiological functions of endogenous cardiotonic steroids.

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“…25 Using antibodies specific for each of these compounds, elevated levels of OB and MBG, as measured by radioimmunoassay of both, have been shown in preeclampsia. 26 As both OB and MBG cross-react with digoxin antibodies, 22 the lowering of blood pressure we observed with DIF could have been due to binding of one or both endogenous cardenolides by the digoxin antibody or possibly, to an as yet unidentified EDLF. It should be noted, however, that in vitro cross reactivity of digoxin antibodies to MBG is about 50 times higher than to OB.…”

Section: Discussionmentioning

confidence: 91%

The hemodynamic effects of intravenous digoxin-binding fab immunoglobulin in severe preeclampsia: a double-blind, randomized, clinical trial

et al. 2009

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Objective: An endogenous digitalis-like factor (EDLF) has been implicated in the pathophysiology of preeclampsia (PE). This hypothesis is supported by two cases of preeclampsia in which administration of digoxin immune Fab (DIF) reduced mean arterial pressure (MAP). Study Design: To study this observation further, we performed a double-blind, placebo-controlled, randomized clinical trial to examine the effects on MAP of intravenous DIF given after delivery in 26 subjects with severe preeclampsia. Treating obstetricians were blinded to subject assignment and were allowed to use standard antihypertensive drugs during the trial. Results: The primary outcome, a significant difference in blood pressure between the two groups over the 24-h period of observation after the intervention, was not supported. However, mean MAP was significantly lower in the DIF-treated subjects for the first 4 h after therapy as compared with controls (P ¼ 0.05). Six subjects (46.2%) in the placebo arm were given conventional antihypertensive medications by their obstetrician for blood pressure >160 mm Hg systolic or >110 mm Hg diastolic, compared with zero subjects in the treatment arm (P ¼ 0.01). A trend towards increased creatinine clearance was observed in DIF-treated subjects (137.6 ± 42.6 versus 104.1 ± 43.4, P ¼ 0.07). Conclusion: These results support the hypothesis that EDLF contributes to the elevated blood pressure in preeclampsia and suggests a possible role for DIF as a treatment for this condition.

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Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia

Cited by 176 publications

References 33 publications

Endogenous digitalis: pathophysiologic roles and therapeutic applications

Endogenous digitalis: pathophysiologic roles and therapeutic applications

Endogenous sodium pump inhibitors, diabetes mellitus and preeclampsia

The hemodynamic effects of intravenous digoxin-binding fab immunoglobulin in severe preeclampsia: a double-blind, randomized, clinical trial

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