Endogenous Na/K-ATPase inhibitors in patients with preeclampsia

Although preeclampsia (PE) is a major cause of maternal and fetal mortality, its pathogenesis is not fully understood. Digitalis-like cardiotonic steroids (CTS) are believed to be involved in the pathophysiology of PE, as illustrated by clinical observations that DIGIBIND, a digoxin antibody which binds CTS, lowers blood pressure in PE. Recently we reported that plasma levels of marinobufagenin (MBG), a vasoconstrictor CTS, are increased fourfold in patients with severe PE. In the present study, we tested whether anti-MBG, or anti-ouabain antibodies, or DIGIBIND can reverse inhibition of erythrocyte Na/K-ATPase (NKA) from patients with mild PE (blood pressure, 149±3/93±3 mm Hg; age, 28±2 years; gestational age, 37±1 weeks). Development of PE was associated with twofold rise in plasma MBG levels (1.58±0.15 vs. 0.80±0.11 nmol/L; P<0.01). The activity of erythrocyte NKA in 12 patients with PE was lower than in 6 normotensive gestational age-matched subjects (1.56±0.18 vs. 3.11±0.16 μmol P_i/ml/hr; P<0.001). In vitro treatment of erythrocytes from PE patients with anti-MBG antibody fully restored the NKA activity (3.26±0.41 μmol P_i/ml/hr; P<0.01). The effects of DIGIBIND was marginally significant (2.53±0.32 μmol P _i/ml/hr), while the anti-ouabain antibody was not effective (2.25±0.25 μmol Pi/ml/hr, P>0.5). The present observations provide evidence for a role for MBG in the pathogenesis of PE, and suggest that antibodies against MBG may be useful in the treatment of this syndrome.