ABSTRACT
BACKGROUND: Preeclampsia is a potentially devastating disorder of hypertension in pregnancy for which there is currently no definitive treatment short of delivery. The bufadienolide, marinobufagenin (MBG), an inhibitor of Na(+)/K(+) ATPase, has been found to be elevated in extracellular fluid volume-expanded hypertensive patients, a condition similar to preeclampsia. Thus, these studies sought to examine the role of MBG in our rat model of preeclampsia. METHODS AND RESULTS: Pregnant female rats were injected intraperitoneally with deoxycorticosterone acetate (DOCA) and given 0.9% saline as drinking water for the duration of their pregnancy. Urinary MBG was measured using a DELFIA immunoassay. Blood pressure was measured via the tail-cuff method. Injections of anti-MBG antibody were given intraperitoneally or intravenously to hypertensive pregnant rats. MBG was given intraperitoneally to pregnant rats. Uterine arterioles were dissected free and their diameters were measured before and after perfusion of MBG, ouabain, or digoxin. MBG was found to be elevated in the pregnant + DOCA + saline (PDS) rats compared to normal pregnant animals. In addition, when PDS rats were injected with anti-MBG antibody, there was a subsequent reduction in blood pressure. Administration of MBG in normal pregnant rats caused an elevation in blood pressure equivalent to the PDS model. Also, uterine vessel measurements showed an increased vasoconstrictive reactivity to MBG in the PDS animals vs. the normal pregnant controls; while no changes were observed with perfusion of digoxin or ouabain at the same concentration. CONCLUSION: These results suggest a relationship between MBG and a syndrome in rats resembling preeclampsia. Armed with these promising results, it would seem logical to further examine the role of MBG in human preeclampsia.
