The role of excessive volume expansion in the pathogenesis of preeclampsia

Preeclampsia is a disorder which is responsible for significant maternal morbidity and mortality as well as fetal wastage. Its pathogenesis remains obscure and its only treatment is the delivery of the placenta and the fetus. Over time it has become clear that this syndrome is not a single disease but a disorder with, most likely, multiple etiologic factors that have a common (or similar) phenotype(s). A leading hypothesis, first developed in the early 1970s, is that the hypertension, proteinuria and intrauterine growth restriction are the result of hypoperfusion of the maternal-fetal unit. However, the early events leading to this deranged circulatory event have not been extensively studied. We hypothesize that at least one of the early pathogenetic events is excessive expansion of the extracellular fluid volume. This leads to persistent elaboration of (a) circulating factor(s) that interfere(s) with remodeling of the decidual vasculature preventing normal placentation from occurring. Our experiments have dealt largely with the role that an endogenous bufadienolide, marinobufagenin (MBG), plays in this pathogenetic process. In this report, we provide evidence for this thesis and point to future studies aimed at testing this hypothesis. These will include evaluating large groups of preeclamptic patients to determine their blood and urinary levels of MBG. Efforts will also be made to determine if there are differences in sodium handling in those patients with elevated levels of MBG, compared to other preeclamptic patients and to normal pregnant subjects.