Antibody to marinobufagenin lowers blood pressure in pregnant rats on a high NaCl intake.
OBJECTIVE
The pathogenesis of pre-eclampsia (PE), a major cause of maternal and fetal mortality, is not fully understood. Digitalis-like sodium pump ligands (SPLs) are believed to be implicated in PE, as illustrated by clinical observations that DIGIBIND, a digoxin antibody that binds SPLs, lowers blood pressure (BP) in PE. We recently reported that plasma levels of marinobufagenin (MBG), a vasoconstrictor SPL, are increased four-fold in patients with PE. In the present study, we tested whether a polyclonal antibody to MBG can lower BP in rats with pregnancy-associated hypertension.


METHODS
Systolic BP (SBP), 24-h renal excretion of MBG and endogenous ouabain (EO), and sodium pump activity in the thoracic aortae were measured in virgin and pregnant Sprague-Dawley rats without and with NaCl supplementation (drinking 1.8% NaCl solution).


RESULTS
NaCl supplementation of virgin rats stimulated renal excretion of MBG by 60%, but not that of EO, and did not change the BP. Compared with virgin rats, the last week of pregnancy in non-NaCl-loaded rats was associated with a decrease in SBP (106 +/- 2 versus 117 +/- 2 mmHg); a moderate increase in renal excretion of MBG (97.6 +/- 4.9 versus 57.4 +/- 7.0 pmoles/24 h) and EO (36.2 +/- 4.3 versus 24.1 +/- 3.2 pmoles/24 h). NaCl-loaded pregnant rats exhibited elevation in SBP (139 +/- 3 mmHg; P < 0.01 versus non-NaCl-loaded pregnant rats), in renal excretion of MBG (160.0 +/- 17.5 pmoles/24 h; P < 0.01 versus non-NaCl-loaded pregnant rats), but not in EO, and showed fetal growth retardation. Administration of the anti-MBG antibody to NaCl-loaded pregnant rats lowered SBP (111 +/- 2 mmHg; P < 0.01) and increased aortic sodium pump activity (144 +/- 3 versus 113 +/- 5 nmol Rb/g per min; P < 0.01 versus non-NaCl-loaded pregnant rats).


CONCLUSIONS
These observations provide evidence that MBG contributes to BP elevation in pregnant rats rendered hypertensive by NaCl supplementation.
Fedorova
Olga V
OV
Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore Maryland, USA.
Kolodkin
Nikolai I
NI
Agalakova
Natalia I
NI
Namikas
Alexandra R
AR
Bzhelyansky
Anton
A
St-Louis
Jean
J
Lakatta
Edward G
EG
Bagrov
Alexei Y
AY
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001794:Blood Pressure; D001835:Body Weight; D002018:Bufanolides / Q000276:immunology* / Q000652:urine; D004326:Drinking; D005260:Female; D046110:Hypertension, Pregnancy-Induced / Q000628:therapy*; D007167:Immunotherapy / Q000379:methods*; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium; D017673:Sodium Chloride, Dietary / Q000494:pharmacology / Q000652:urine
D000906:Antibodies; D002018:Bufanolides; D017673:Sodium Chloride, Dietary; C093896:marinobufagenin; D012964:Sodium