Abstract 315: Supression of Aldosterone and Progesterone in Preeclampsia: Role of Marinobufagenin: A Translational Approach
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Preeclampsia (preE) is a hypertensive disorder of pregnancy. In an animal model of preE, we have shown that the urinary excretion of marinobufagenin (MBG) is elevated prior to the development of hypertension and proteinuria. Several research groups provided evidence for reduced aldosterone (Aldo) and progesterone (Prog) availability in preE. This study focuses on the alterations in Aldo & Prog in a rat model of preE, in vitro study and in preE patients. Three groups of animals were studied: normal pregnant (NP, n = 9); pregnant rats that received weekly injections of desoxycorticosterone acetate and saline drinking water (PDS; preE rat model, n = 9); and NP rats injected with MBG (7.65 g/kg/d, NPM, n = 8). The plasma and urinary levels of Aldo were assayed in all groups. To see the effect of MBG in the secretion of Aldo, adrenal cells were treated with DMSO (vehicle), 0.1, 1, 10 or 100 nM MBG. The levels of Aldo & Prog in the culture media of MBG-treated adrenal cells and in cell lysates were measured by ELISA. We recruited 17 PreE and 23 normally pregnant patients at Scott & White hospital. Aldo, Prog and MBG levels were assayed in plasma samples by ELISA. Both plasma and urinary levels of Aldo (NP: 578.5 152.4, PDS: 379.5 89.6, NPM: 348.7 91.3 pg/mL for plasma; NP: 86.7 10.7, PDS: 52.0 5.2, NPM: 58.9 6 for urine, p<0.05 for each case) & Prog (NP: 31.5 2.9, PDS: 18.6 2.1, NPM: 16.5 91.3 ng/mL for plasma; NP: 6.5 0.5, PDS: 3.5 0.4, NPM: 3.2 0.5 for urine, p<0.05 for each case) were significantly lower in PDS and NPM rats compared to NP. MBG 1 nM significantly decreased the secretion of Aldo in MBG- treated adrenal cells when compared to the vehicle-treated cells. The mean plasma Aldo of 398.6 115.8 pg/mL and Prog of 46.2 9.5 ng/ml in PreE patients were significantly suppressed (p<0.05) from 548.4 137.5 pg/mL and 82.5 13.6 ng/l, respectively, in NP women. On the contrary, plasma MBG was significantly higher (p<0.05) in preE compared to NP (preE: 59 17 & NP: 12 2 pg/mL). These data suggest that Aldo & Prog are paradoxically concealed in PreE. Moreover, it has been suggested that MBG is involved in the downregulation of Aldo & Prog expression in preE rat model and in in vitro adrenal cells. This study provides new evidence that MBG plays a key role in the suppression of Aldo & Prog in PreE.
