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 micromol Pi/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 micromol Pi/ml/hr; P<0.01). The effects of DIGIBIND was marginally significant (2.53 +/- 0.32 micromol Pi/ml/hr), while the anti-ouabain antibody was not effective (2.25 +/- 0.25 micromol 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.
Averina
I V
IV
Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Tapilskaya
N I
NI
Reznik
V A
VA
Frolova
E V
EV
Fedorova
O V
OV
Lakatta
E G
EG
Bagrov
A Y
AY
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D002018:Bufanolides / Q000097:blood* / Q000276:immunology; D004077:Digoxin / Q000097:blood* / Q000276:immunology; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D010042:Ouabain / Q000097:blood* / Q000276:immunology; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000906:Antibodies; D002018:Bufanolides; C093896:marinobufagenin; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase