Circulating bufodienolide and cardenolide sodium pump inhibitors in preeclampsia.
OBJECTIVE
To determine plasma levels of the endogenous bufodienolide Na+/K+ ATPase inhibitor, marinobufagenin-like factor (MBG), in normotensive pregnancy and in preeclampsia, to compare changes of MBG with that of ouabain-like compound (OLC), and to characterize the purified MBG immunoreactive factor from preeclamptic plasma.


METHODS
Consecutive sample study. The levels of MBG and OLC compounds were measured in extracted plasma by solid phase fluoroimmunoassays. MBG and ouabain immunoreactive materials were partially purified from preeclamptic plasma via reverse-phase high-performance liquid chromatography (HPLC) and studied for their ability to cross react with MBG and ouabain antibodies, and to inhibit the Na+/K+ ATPase from human mesenteric arteries. Vasoconstrictor effect of authentic MBG was studied in isolated rings of human umbilical arteries.


RESULTS
In 11 nonpregnant control individuals, plasma concentrations of MBG and OLC were 0.190+/-0.04 nmol/l and 0.297+/-0.037 nmol/l, respectively. In the third trimester of noncomplicated pregnancy (n = 6), plasma MBG increased (0.625+/-0.067 nmol/l, P<0.05), and OLC did not (0.32+/-0.07 nmol/l). In 15 patients with preeclampsia, plasma levels of both MBG and OLC increased dramatically (2.63+/-0.10 nmol/l and 0.697+/-0.16 nmol/l, respectively, P<0.01 versus both control groups). When fractionated by reverse phase HPLC, OLC was eluted by 18% acetonitrile, and MBG by 48% acetonitrile. Serially diluted samples of MBG and OLC immunoreactive materials from HPLC fractions reacted with MBG and ouabain antibody in solid phase immunoassay in a concentration dependent fashion. Authentic MBG caused contractile responses of isolated rings of human mesenteric arteries in a concentration-dependent manner. Similarly to the authentic MBG, HPLC purified MBG immunoreactive material from preeclamptic plasma inhibited Na+/K+ ATPase purified from human mesenteric artery.


CONCLUSIONS
Our observations demonstrate the coexistence of two endogenous cardiotonic steroids in preeclamptic plasma, a more polar OLC and a less polar MBG-like compound. Substantial increases in plasma OLC and MBG immunoreactivity in preeclampsia, along with the vasoconstrictor properties of authentic MBG and Na+,K+ ATPase inhibitory activity of human MBG immunoreactive factor, suggest, that in preeclampsia, plasma concentrations of MBG are enough to substantially inhibit the sodium pump in cardiovascular tissues, and are in accordance with the views attributing endogenous digitalis-like factors a pathogenic role in the preeclamptic hypertension.
Lopatin
D A
DA
DO Ott Institute of Obstetrics and Gynaecology, St. Petersburg, Russia.
Ailamazian
E K
EK
Dmitrieva
R I
RI
Shpen
V M
VM
Fedorova
O V
OV
Doris
P A
PA
Bagrov
A Y
AY
D000328:Adult; D000818:Animals; D001001:Anura; D002018:Bufanolides / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D002298:Cardenolides / Q000097:blood* / Q000276:immunology; D002301:Cardiac Glycosides / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D010042:Ouabain / Q000276:immunology / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D002018:Bufanolides; D002298:Cardenolides; D002301:Cardiac Glycosides; D007140:Immunoglobulin Fab Fragments; C050199:digoxin antibodies Fab fragments; C093896:marinobufagenin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase