Marinobufagenin, an endogenous Na/K-ATPase inhibitor, in preeclampsia

Abstract

Although preeclampsia (PE) is a major cause of maternal and fetal mortality, its pathogenesis is not fully understood. Endogenous digitalis-like sodium pump ligands (SPLs) are believed to be involved in pathophysiology of PE, as illustrated by clinical observations that DIGIBIND, a digoxin antibody which binds SPLs. Lowers blood pressure (BP) in PE. Recently we reported that plasma levels of marinobufagenin (MBG), a vasoconstrictor SPL, are increased four-fold in patients with severe PE. In the present study, we tested whether polyclonal antibodies to MBG and ouabain, and DIGIBIND can reverse inhibition of erythrocyte Na/K-ATPase (NKN) from patients with mild PE. Development of PE was associated with two-told rise in plasma MBG levels (1.58 ± 0.15 vs. 0.80 ± 0.11 nmol/E: P < 0.01). The activity of erythrocyte NKA in 12 patients with PE (BP, 149 ± 3 / 93 ± 3 mm Hg; 28 ± 2years; gestational age, 37 ± 1 weeks) was lower, than in 6 normotensive gestational age-matched subjects (1.56 ± 0.18 vs. 3.11 ± 0.16 umol Pi/ml/hr; P < 001). In vitro treatment of erythrocytes from PE patients with anti-MBG antibody hilly restored the NKA activity (3.26 ± 0.41 umol Pi/ml/hr; P < 0.01), the effects of DIGIBIND was marginally significant (2.53 ± 0.32 pmol Pi/ml/hr), while anti-ouabain antibody was not effective (2.25 ± 0.25 umol Pi/ml/hr, P > 0.5) were less effective. Our present observations provide evidence for a role of MBG in pathogenesis of PE, and suggest that antibodies against MBG may be used to treat the syndrome.